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1.
ACS Appl Energy Mater ; 7(17): 7349-7361, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39268392

RESUMO

Although lithium-sulfur (Li-S) batteries offer a high theoretical energy density, shuttling of dissolved sulfur and polysulfides is a major factor limiting the specific capacity, energy density, and cyclability of Li-S batteries with a liquid electrolyte. Cathode host materials with a microstructure to restrict the migration of active material may not totally eliminate the shuttling effect or may create additional problems that limit the full dissolution and redox conversion of all active cathode materials. Selecting a cathode coating binder with a multifunctional role offers a universal solution suitable for various cathode hosts. PEDOT:PSS is investigated as such a binder in this study via experimental testing and material characterization as well as multiscale modeling. The study is based on Li-S cells with a sulfur cathode in hollow porous particles as the cathode host and the 10 wt % PEDOT:PSS binder and electrolyte 1 M LiTFSI in 1:1 DOL:DME 1:1 v/v. A reference supercapacitor cell with the same electrolyte and electrodes comprising a coating of the same hollow porous particles and 10 wt % PEDOT:PSS revealed the pseudocapacitive effect of PEDOT:PSS following a surface redox mechanism that dominates the charge phase, which is equivalent to the discharge phase of the Li-S battery cell. A multipore continuum model for supercapacitors and Li-S cells is extended to incorporate the pseudocapacitive effects of PEDOT:PSS with the Li+ ions and the adsorption effects of PEDOT:PSS with respect to sulfur and lithium sulfides in Li-S cells, with the adsorption energies determined via molecular and ab initio simulations in this study. Experimental data and predictions of multiscale simulations concluded a 7-9% extension of the specific capacity of Li-S battery cells due to the surface redox effect of PEDOT:PSS and elimination of lithium sulfides from the anode by slowing down their migration and shuttling via their adsorption by the PEDOT:PSS binder.

3.
Radiology ; 312(2): e233039, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-39105637

RESUMO

Background Clinical decision making and drug development for fibrostenosing Crohn disease is constrained by a lack of imaging definitions, scoring conventions, and validated end points. Purpose To assess the reliability of MR enterography features to describe Crohn disease strictures and determine correlation with stricture severity. Materials and Methods A retrospective study of patients with symptomatic terminal ileal Crohn disease strictures who underwent MR enterography at tertiary care centers (Cleveland Clinic: September 2013 to November 2020; Mayo Clinic: February 2008 to March 2019) was conducted by using convenience sampling. In the development phase, blinded and trained radiologists independently evaluated 26 MR enterography features from baseline and follow-up examinations performed more than 6 months apart, with no bowel resection performed between examinations. Follow-up examinations closest to 12 months after baseline were selected. Reliability was assessed using the intraclass correlation coefficient (ICC). In the validation phase, after five features were redefined, reliability was re-estimated in an independent convenience sample using baseline examinations. Multivariable linear regression analysis identified features with at least moderate interrater reliability (ICC ≥0.41) that were independently associated with stricture severity. Results Ninety-nine (mean age, 40 years ± 14 [SD]; 50 male) patients were included in the development group and 51 (mean age, 45 years ± 16 [SD]; 35 female) patients were included in the validation group. In the development group, nine features had at least moderate interrater reliability. One additional feature demonstrated moderate reliability in the validation group. Stricture length (ICC = 0.85 [95% CI: 0.75, 0.91] and 0.91 [95% CI: 0.75, 0.96] in development and validation phase, respectively) and maximal associated small bowel dilation (ICC = 0.74 [95% CI: 0.63, 0.80] and 0.73 [95% CI: 0.58, 0.87] in development and validation group, respectively) had the highest interrater reliability. Stricture length, maximal stricture wall thickness, and maximal associated small bowel dilation were independently (regression coefficients, 0.09-3.97; P < .001) associated with stricture severity. Conclusion MR enterography definitions and scoring conventions for reliably assessing features of Crohn disease strictures were developed and validated, and feature correlation with stricture severity was determined. © RSNA, 2024 Supplemental material is available for this article. See also the article by Rieder and Ma et al in this issue. See also the editorial by Galgano and Summerlin in this issue.


Assuntos
Doença de Crohn , Imageamento por Ressonância Magnética , Humanos , Doença de Crohn/diagnóstico por imagem , Feminino , Masculino , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Adulto , Reprodutibilidade dos Testes , Constrição Patológica/diagnóstico por imagem , Pessoa de Meia-Idade
4.
Radiology ; 312(2): e233038, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-39105638

RESUMO

Background Standardized methods to measure and describe Crohn disease strictures at CT enterography are needed to guide clinical decision making and for use in therapeutic studies. Purpose To assess the reliability of CT enterography features to describe Crohn disease strictures and their correlation with stricture severity. Materials and Methods A retrospective study was conducted in 43 adult patients with symptomatic terminal ileal Crohn disease strictures who underwent standard-of-care CT enterography at a tertiary care center at the Cleveland Clinic between January 2008 and August 2016. After training on standardized definitions, four abdominal radiologists blinded to all patient information assessed imaging features (seven continuous measurements and nine observations) of the most distal ileal stricture in two separate sessions (separated by ≥2 weeks) in random order. Features with an interrater intraclass correlation coefficient (ICC) of 0.41 or greater (ie, moderate reliability or better) were considered reliable. Univariable and multivariable linear regression analysis identified reliable features associated with a visual analog scale of overall stricture severity. Significant reliable features were assessed as components of a CT enterography-based model to quantitate stricture severity. Results Examinations in 43 patients (mean age, 52 years ± 16 [SD]; 23 female) were evaluated. Five continuous measurements and six observations demonstrated at least moderate interrater reliability (interrater ICC range, 0.42 [95% CI: 0.25, 0.57] to 0.80 [95% CI: 0.67, 0.88]). Of these, 10 were univariably associated with stricture severity, and three continuous measurements-stricture length (interrater ICC, 0.64 [95% CI: 0.42, 0.81]), maximal associated small bowel dilation (interrater ICC, 0.80 [95% CI: 0.67, 0.88]), and maximal stricture wall thickness (interrater ICC, 0.50 [95% CI: 0.34, 0.62])-were independently associated (P value range, <.001 to .003) with stricture severity in a multivariable model. These three measurements were used to derive a well-calibrated (optimism-adjusted calibration slope = 1.00) quantitative model of stricture severity. Conclusion Standardized CT enterography measurements and observations can reliably describe terminal ileal Crohn disease strictures. Stricture length, maximal associated small bowel dilation, and maximal stricture wall thickness are correlated with stricture severity. © RSNA, 2024 Supplemental material is available for this article. See also the article by Rieder et al in this issue. See also the editorial by Galgano and Summerlin in this issue.


Assuntos
Doença de Crohn , Tomografia Computadorizada por Raios X , Humanos , Doença de Crohn/diagnóstico por imagem , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Reprodutibilidade dos Testes , Constrição Patológica/diagnóstico por imagem , Adulto , Idoso
5.
Proteomes ; 12(3)2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39189262

RESUMO

Capsular contracture (CC) is one of the most common postoperative complications associated with breast implant-associated infections. The mechanisms that lead to CC remain poorly understood. Plasma is an ideal biospecimen for early proteomics biomarker discovery. However, as high-abundance proteins mask signals from low-abundance proteins, identifying novel or specific proteins as biomarkers for a particular disease has been hampered. Here, we employed depletion of high-abundance plasma proteins followed by Tandem Mass Tag (TMT)-based quantitative proteomics to compare 10 healthy control patients against 10 breast implant CC patients. A total of 450 proteins were identified from these samples. Among them, 16 proteins were significantly differentially expressed in which 5 proteins were upregulated and 11 downregulated in breast implant CC patients compared to healthy controls. Gene Ontology enrichment analysis revealed that proteins related to cell, cellular processes and catalytic activity were highest in the cellular component, biological process, and molecular function categories, respectively. Further, pathway analysis revealed that inflammatory responses, focal adhesion, platelet activation, and complement and coagulation cascades were enriched pathways. The differentially abundant proteins from TMT-based quantitative proteomics have the potential to provide important information for future mechanistic studies and in the development of breast implant CC biomarkers.

6.
iScience ; 27(7): 110198, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39092172

RESUMO

Male subfertility or infertility is a common condition often characterized by men producing a low number of sperm with poor quality. To gain insight into this condition, we performed a quantitative proteomic analysis of semen samples obtained from infertile and fertile men. At least 6 proteins showed significant differences in regulation of alternatively spliced isoforms. To investigate this link between aberrant alternative splicing and production of poor-quality spermatozoa, we overexpressed the hnrnpH/F-orthologue Glorund (Glo) in Drosophila, which was also found to be abundant in poor quality human sperm. Transgenic animals produced low numbers of morphologically defective spermatozoa and aberrant formation of the "dense body," an organelle akin to the mammalian manchette. Furthermore, fertility trials demonstrated that transgenic flies were either completely infertile or highly subfertile. These findings suggest that dysregulation of hnrnpH/F is likely to result in the production of low-quality semen, leading to subfertility or infertility in men.

7.
Sci Rep ; 14(1): 20159, 2024 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-39215164

RESUMO

Capacitation is an essential post-testicular maturation event endowing spermatozoa with fertilizing capacity within the female reproductive tract, significant for fertility, reproductive health, and contraception. By using a human-relevant large animal model, the domestic boar, this study focuses on furthering our understanding of the involvement of the ubiquitin-proteasome system (UPS) in sperm capacitation. The UPS is a universal, evolutionarily conserved, cellular proteome-wide degradation and recycling machinery, that has been shown to play a significant role in reproduction during the past two decades. Herein, we have used a bottom-up proteomic approach to (i) monitor the capacitation-related changes in the sperm protein levels, and (ii) identify the targets of UPS regulation during sperm capacitation. Spermatozoa were capacitated under proteasomal activity-permissive and inhibiting conditions and extracted sperm proteins were subjected to high-resolution mass spectrometry. We report that 401 individual proteins differed at least two-fold in abundance (P < 0.05) after in vitro capacitation (IVC) and 13 proteins were found significantly different (P < 0.05) between capacitated spermatozoa with proteasomal inhibition compared to the vehicle control. These proteins were associated with biological processes including sperm capacitation, sperm motility, metabolism, binding to zona pellucida, and proteasome-mediated catabolism. Changes in RAB2A, CFAP161, and TTR during IVC were phenotyped by immunocytochemistry, image-based flow cytometry, and Western blotting. We conclude that (i) the sperm proteome is subjected to extensive remodeling during sperm capacitation, and (ii) the UPS has a narrow range of distinct protein substrates during capacitation. This knowledge highlights the importance of the UPS in sperm capacitation and offers opportunities to identify novel pharmacological targets to modulate sperm fertilizing ability for the benefit of human reproductive health, assisted reproductive therapy, and contraception, as well as reproductive management in food animal agriculture.


Assuntos
Complexo de Endopeptidases do Proteassoma , Proteômica , Capacitação Espermática , Espermatozoides , Ubiquitina , Capacitação Espermática/fisiologia , Animais , Masculino , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitina/metabolismo , Suínos , Espermatozoides/metabolismo , Espermatozoides/fisiologia , Proteômica/métodos , Proteoma/metabolismo
8.
Reproduction ; 168(4)2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39056485

RESUMO

In Brief: In many mammals, the lipid platelet-activating factor (PAF) has important functions in female reproduction and fertility. This study shows that PAF is present in the reproductive tissues of mares and is involved in processes related to ovulation and early pregnancy. Abstract: Platelet-activating factor (PAF) has been implicated in a number of reproductive processes ranging from ovulation to embryo motility but has not been widely explored in the mare. To identify the presence and examine the role of PAF in the equine periconception processes, targeted mass spectrometry coupled with chromatographic separation was performed on equine follicular fluid (FF), and PAF was quantitatively detected. Subsequently, untargeted high-resolution mass spectrometry-based lipidomic analysis was carried out to quantify PAF in different-sized pre-ovulatory follicles, whereby different molecular species of PAF, PAF (14:0) and PAF (16:1), were both seen to be increasing with follicle diameter. These findings suggest that PAF within FF is increasing as preovulatory follicles approach ovulation. Additionally, immunofluorescence staining identified the PAF receptor in the luminal pericellular, apical, and basal aspect of equine oviductal epithelial cells. Lastly, an equine oviductal epithelial organoid model was generated and showed that the addition of PAF significantly increased the ciliary beat frequency (CBF) (Hz), an action consistent with a role for PAF in embryo migration. It is proposed that the local action of PAF on the ciliated cells of the oviduct propels both the oocyte and the conceptus towards the uterus. In the mare, it appears that PAF is a contributor during the periconception period, potentially being a mediator in the mechanisms of ovulation and in the dialogue of very early pregnancy.


Assuntos
Ovulação , Fator de Ativação de Plaquetas , Animais , Cavalos/fisiologia , Feminino , Fator de Ativação de Plaquetas/metabolismo , Fator de Ativação de Plaquetas/farmacologia , Gravidez , Ovulação/fisiologia , Folículo Ovariano/metabolismo , Folículo Ovariano/fisiologia , Líquido Folicular/metabolismo , Fertilização/fisiologia
9.
J Pharm Pract ; : 8971900241262382, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39024019

RESUMO

Background: Initiation of sacubitril-valsartan and mineralocorticoid receptor antagonists (MRA) during hospitalization for acute decompensated heart failure (ADHF) may be an ideal time to optimize guideline-directed medical therapy. However, there is limited research assessing the safety of combining these agents in the hospital. Methods: This was a multi-center, retrospective, propensity-score matched cohort study performed at 7 acute-care hospitals within a large health care system. All adult patients admitted with ADHF between January 1, 2019 to December 31, 2021 who received sacubitril-valsartan with MRA (MRA group) or without MRA (non-MRA group) and had a left ventricular ejection fraction (LVEF) < 40% were included in the study. Results: 220 patients were screened during the study time frame with 179 meeting inclusion criteria. Following propensity-score matching, 50 patients in the MRA group were matched to 50 patients in the non-MRA group. The overall incidence of adverse drug reactions (ADRs) was 24% in the non-MRA group compared to 20% in the MRA group (P = .629). There was a significantly greater incidence of hyperkalemia in the MRA group (0% vs 10%; P = .022). None of the patients in the non-MRA group were readmitted within 30 days due to an ADR compared to 6% in the MRA group (P = .079). Conclusion: The addition of spironolactone to sacubitril-valsartan in the hospital setting following stabilization of ADHF did not lead to a significantly greater incidence of overall ADRs, but patients were more likely to develop hyperkalemia and there was a numerically higher incidence of 30-day readmissions due to ADRs.

10.
Clin Transl Med ; 14(6): e1734, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38888967

RESUMO

BACKGROUND: Sporadic parathyroid adenoma (PA) is the most common cause of hyperparathyroidism, yet the mechanisms involved in its pathogenesis remain incompletely understood. METHODS: Surgically removed PA samples, along with normal parathyroid gland (PG) tissues that were incidentally dissected during total thyroidectomy, were analysed using single-cell RNA-sequencing with the 10× Genomics Chromium Droplet platform and Cell Ranger software. Gene set variation analysis was conducted to characterise hallmark pathway gene signatures, and single-cell regulatory network inference and clustering were utilised to analyse transcription factor regulons. Immunohistochemistry and immunofluorescence were performed to validate cellular components of PA tissues. siRNA knockdown and gene overexpression, alongside quantitative polymerase chain reaction, Western blotting and cell proliferation assays, were conducted for functional investigations. RESULTS: There was a pervasive increase in gene transcription in PA cells (PACs) compared with PG cells. This is associated with high expression of histone-lysine N-methyltransferase 2A (KMT2A). High KMT2A levels potentially contribute to promoting PAC proliferation through upregulation of the proto-oncogene CCND2, which is mediated by the transcription factors signal transducer and activator of transcription 3 (STAT3) and GATA binding protein 3 (GATA3). PA tissues are heavily infiltrated with myeloid cells, while fibroblasts, endothelial cells and macrophages in PA tissues are commonly enriched with proinflammatory gene signatures relative to their counterparts in PG tissues. CONCLUSIONS: We revealed the previously underappreciated involvement of the KMT2A‒STAT3/GATA3‒CCND2 axis and chronic inflammation in the pathogenesis of PA. These findings underscore the therapeutic promise of KMT2A inhibition and anti-inflammatory strategies, highlighting the need for future investigations to translate these molecular insights into practical applications. HIGHLIGHTS: Single-cell RNA-sequencing reveals a transcriptome catalogue comparing sporadic parathyroid adenomas (PAs) with normal parathyroid glands. PA cells show a pervasive increase in gene expression linked to KMT2A upregulation. KMT2A-mediated STAT3 and GATA3 upregulation is key to promoting PA cell proliferation via cyclin D2. PAs exhibit a proinflammatory microenvironment, suggesting a potential role of chronic inflammation in PA pathogenesis.


Assuntos
Adenoma , Histona-Lisina N-Metiltransferase , Inflamação , Neoplasias das Paratireoides , Humanos , Neoplasias das Paratireoides/genética , Neoplasias das Paratireoides/metabolismo , Neoplasias das Paratireoides/patologia , Adenoma/genética , Adenoma/metabolismo , Adenoma/patologia , Inflamação/genética , Inflamação/metabolismo , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/metabolismo , Proto-Oncogene Mas , Proliferação de Células/genética
11.
Nat Rev Gastroenterol Hepatol ; 21(8): 572-584, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38831007

RESUMO

Fibrostenosis of the small bowel is common in patients with Crohn's disease. No consensus recommendations on definition, diagnosis and management in clinical practice are currently available. In this Consensus Statement, we present a clinical practice RAND/UCLA appropriateness study on the definition, diagnosis and clinical management of fibrostenosing Crohn's disease. It was conducted by a panel of 28 global experts and one patient representative. Following a systematic literature review, 526 candidate items grouped into 136 questions were generated and subsequently evaluated for appropriateness. Strictures are best defined as wall thickening, luminal narrowing and prestenotic dilation. Cross-sectional imaging is required for accurate diagnosis of fibrostenosing Crohn's disease, and it is recommended before making treatment decisions. It should also assess the degree of inflammation in the bowel wall. Multiple options for medical anti-inflammatory, endoscopic and surgical therapies were suggested, including follow-up strategies following therapy. This Consensus Statement supports clinical practice through providing guidance on definitions, diagnosis and therapeutic management of patients with fibrostenosing small bowel Crohn's disease.


Assuntos
Consenso , Doença de Crohn , Intestino Delgado , Doença de Crohn/diagnóstico , Doença de Crohn/terapia , Humanos , Intestino Delgado/patologia , Fibrose
12.
J Crohns Colitis ; 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38761165

RESUMO

BACKGROUND & AIMS: Non-invasive cross-sectional imaging via magnetic resonance enterography (MRE) offers excellent accuracy for the diagnosis of stricturing complications in Crohn's disease (CD) but is limited in determining the degrees of fibrosis and inflammation within a stricture. We developed and validated a radiomics-based machine-learning model for separately characterizing the degree of histopathologic inflammation and fibrosis in CD strictures and compared it to centrally read visual radiologist scoring of MRE. METHODS: This single center, cross-sectional study, included 51 CD patients (n=34 for discovery; n=17 for validation) with terminal ileal strictures confirmed on diagnostic MRE within 15 weeks of resection. Histopathological specimens were scored for inflammation and fibrosis and spatially linked with corresponding pre-surgical MRE sequences. Annotated stricture regions on MRE were scored visually by radiologists as well as underwent 3D radiomics-based machine learning analysis; both evaluated against histopathology. RESULTS: Two distinct sets of radiomic features capturing textural heterogeneity within strictures were linked with each of severe inflammation or severe fibrosis across both discovery (area under the curve (AUC)=0.69, 0.83) and validation (AUCs=0.67,0.78) cohorts. Radiologist visual scoring had an AUC=0.67 for identifying severe inflammation and AUC=0.35 for severe fibrosis. Use of combined radiomics and radiologist scoring robustly augmented identification of severe inflammation (AUC=0.79) and modestly improved assessment of severe fibrosis (AUC=0.79 for severe fibrosis) over individual approaches. CONCLUSIONS: Radiomic features of CD strictures on MRE can accurately identify severe histopathologic inflammation and severe histopathologic fibrosis, as well as augment performance of radiologist visual scoring in stricture characterization.

13.
Cancer Res ; 84(9): 1460-1474, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38593213

RESUMO

Patients with triple-negative breast cancer (TNBC) have a poor prognosis due to the lack of effective molecular targets for therapeutic intervention. Here we found that the long noncoding RNA (lncRNA) MILIP supports TNBC cell survival, proliferation, and tumorigenicity by complexing with transfer RNAs (tRNA) to promote protein production, thus representing a potential therapeutic target in TNBC. MILIP was expressed at high levels in TNBC cells that commonly harbor loss-of-function mutations of the tumor suppressor p53, and MILIP silencing suppressed TNBC cell viability and xenograft growth, indicating that MILIP functions distinctively in TNBC beyond its established role in repressing p53 in other types of cancers. Mechanistic investigations revealed that MILIP interacted with eukaryotic translation elongation factor 1 alpha 1 (eEF1α1) and formed an RNA-RNA duplex with the type II tRNAs tRNALeu and tRNASer through their variable loops, which facilitated the binding of eEF1α1 to these tRNAs. Disrupting the interaction between MILIP and eEF1α1 or tRNAs diminished protein synthesis and cell viability. Targeting MILIP inhibited TNBC growth and cooperated with the clinically available protein synthesis inhibitor omacetaxine mepesuccinate in vivo. Collectively, these results identify MILIP as an RNA translation elongation factor that promotes protein production in TNBC cells and reveal the therapeutic potential of targeting MILIP, alone and in combination with other types of protein synthesis inhibitors, for TNBC treatment. SIGNIFICANCE: LncRNA MILIP plays a key role in supporting protein production in TNBC by forming complexes with tRNAs and eEF1α1, which confers sensitivity to combined MILIP targeting and protein synthesis inhibitors.


Assuntos
Proliferação de Células , Fator 1 de Elongação de Peptídeos , Biossíntese de Proteínas , RNA Longo não Codificante , RNA de Transferência , Neoplasias de Mama Triplo Negativas , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Humanos , Feminino , RNA de Transferência/genética , RNA de Transferência/metabolismo , Animais , Camundongos , Fator 1 de Elongação de Peptídeos/metabolismo , Fator 1 de Elongação de Peptídeos/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus , Regulação Neoplásica da Expressão Gênica
14.
Sci Rep ; 14(1): 8874, 2024 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632415

RESUMO

One of the major consequences of the COVID-19 pandemic has been the significant incidence of persistent fatigue following resolution of an acute infection (i.e. post-COVID fatigue). We have shown previously that, in comparison to healthy controls, those suffering from post-COVID fatigue exhibit changes in muscle physiology, cortical circuitry, and autonomic function. Whether these changes preceded infection, potentially predisposing people to developing post-COVID fatigue, or whether the changes were a consequence of infection was unclear. Here we present results of a 12-month longitudinal study of 18 participants from the same cohort of post-COVID fatigue sufferers to investigate these correlates of fatigue over time. We report improvements in self-perception of the impact of fatigue via questionnaires, as well as significant improvements in objective measures of peripheral muscle fatigue and autonomic function, bringing them closer to healthy controls. Additionally, we found reductions in muscle twitch tension rise times, becoming faster than controls, suggesting that the improvement in muscle fatigability might be due to a process of adaptation rather than simply a return to baseline function.


Assuntos
COVID-19 , Humanos , Seguimentos , Estudos Longitudinais , Pandemias , Fasciculação
15.
Life Sci Alliance ; 7(6)2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38570187

RESUMO

The transition zone is a specialised gate at the base of cilia/flagella, which separates the ciliary compartment from the cytoplasm and strictly regulates protein entry. We identified a potential new regulator of the male germ cell transition zone, CEP76. We demonstrated that CEP76 was involved in the selective entry and incorporation of key proteins required for sperm function and fertility into the ciliary compartment and ultimately the sperm tail. In the mutant, sperm tails were shorter and immotile as a consequence of deficits in essential sperm motility proteins including DNAH2 and AKAP4, which accumulated at the sperm neck in the mutant. Severe annulus, fibrous sheath, and outer dense fibre abnormalities were also detected in sperm lacking CEP76. Finally, we identified that CEP76 dictates annulus positioning and structure. This study suggests CEP76 as a male germ cell transition zone protein and adds further evidence to the hypothesis that the spermatid transition zone and annulus are part of the same functional structure.


Assuntos
Infertilidade Masculina , Cauda do Espermatozoide , Humanos , Masculino , Cauda do Espermatozoide/metabolismo , Motilidade dos Espermatozoides/genética , Sêmen , Infertilidade Masculina/genética , Infertilidade Masculina/metabolismo , Mutação/genética
16.
Nanomaterials (Basel) ; 14(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38607135

RESUMO

This study considers the influence of purity and surface area on the thermal and oxidation properties of hexagonal boron nitride (h-BN) nanoplatelets, which represent crucial factors in high-temperature oxidizing environments. Three h-BN nanoplatelet-based materials, synthesized with different purity levels and surface areas (~3, ~56, and ~140 m2/g), were compared, including a commercial BN reference. All materials were systematically analyzed by various characterization techniques, including gas pycnometry, scanning electron microscopy, X-ray diffraction, Fourier-transform infrared radiation, X-ray photoelectron spectroscopy, gas sorption analysis, and thermal gravimetric analysis coupled with differential scanning calorimetry. Results indicated that the thermal stability and oxidation resistance of the synthesized materials were improved by up to ~13.5% (or by 120 °C) with an increase in purity. Furthermore, the reference material with its high purity and low surface area (~4 m2/g) showed superior performance, which was attributed to the minimized reactive sites for oxygen diffusion due to lower surface area availability and fewer possible defects, highlighting the critical roles of both sample purity and accessible surface area in h-BN thermo-oxidative stability. These findings highlight the importance of focusing on purity and surface area control in developing BN-based nanomaterials, offering a path to enhance their performance in extreme thermal and oxidative conditions.

17.
Aliment Pharmacol Ther ; 59(8): 928-940, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436124

RESUMO

BACKGROUND: Stricturing Crohn's disease (CD) occurs most commonly in the terminal ileum and poses a clinical problem. Cross-sectional imaging modalities such as intestinal ultrasound (IUS), computed tomography enterography (CTE), and magnetic resonance enterography (MRE) allow for assessment of the entire bowel wall and associated peri-enteric findings. Radiologic definitions of strictures have been developed for CTE and MRE; their reliability and responsiveness are being evaluated in index development programs. A comprehensive assessment strategy for strictures using IUS is needed. AIMS: To provide a detailed summary of definitions, diagnosis and monitoring of strictures on IUS as well as technical aspects of image acquisition. METHODS: We searched four databases up to 6 January 2024. Two-stage screening was done in duplicate. We assessed risk of bias using QUADAS-2. RESULTS: There were 56 studies eligible for inclusion. Definitions for strictures on IUS are heterogeneous, but the overall accuracy for diagnosis of strictures is high. The capability of IUS for characterising inflammation versus fibrosis in strictures is not accurate enough to be used in clinical practice or trials. We summarise definitions for improvement of strictures on IUS, and discuss parameters for image acquisition and standardisation. CONCLUSIONS: This systematic review is the first step for a structured program to develop a stricture IUS index for CD.


Assuntos
Doença de Crohn , Obstrução Intestinal , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/diagnóstico por imagem , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/patologia , Reprodutibilidade dos Testes , Intestinos/patologia , Imageamento por Ressonância Magnética/métodos
18.
J Med Syst ; 48(1): 24, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38386137

RESUMO

BACKGROUND: Intraoperative neurophysiological monitoring (IOM) is a valuable adjunct for neurosurgical operative techniques, and has been shown to improve clinical outcomes in cranial and spinal surgery. It is not necessarily provided by NHS hospitals so may be outsourced to private companies, which are expensive and at cost to the NHS trusts. We discuss the benefits and challenges of developing an in-house service. METHODS: We surveyed NHS neurosurgical departments across England regarding their expenditure on IOM over the period January 2018 - December 2022 on cranial neurosurgery and spinal surgery. Out of 24 units, all responded to our Freedom of Information requests and 21 provided data. The standard NHS England salary of NHS staff who would normally be involved in IOM, including physiologists and doctors, was also compiled for comparison. RESULTS: The total spend on outsourced IOM, across the units who responded, was over £8 million in total for the four years. The annual total increased, between 2018 and 2022, from £1.1 to £3.5 million. The highest single unit yearly spend was £568,462. This is in addition to salaries for staff in neurophysiology departments. The mean NHS salaries for staff is also presented. CONCLUSION: IOM is valuable in surgical decision-making, planning, and technique, having been shown to lead to fewer patient complications and shorter length of stay. Current demand for IOM outstrips the internal NHS provision in many trusts across England, leading to outsourcing to private companies. This is at significant cost to the NHS. Although there is a learning curve, there are many benefits to in-house provision, such as stable working relationships, consistent methods, training of the future IOM workforce, and reduced long-term costs, which planned expansion of NHS services may provide.


Assuntos
Neurocirurgia , Humanos , Monitorização Intraoperatória , Inglaterra , Gastos em Saúde , Hospitais
19.
Pflugers Arch ; 476(5): 847-859, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38421407

RESUMO

Increases in the current threshold occur in optic nerve axons with the application of infra-red laser light, whose mechanism is only partly understood. In isolated rat optic nerve, laser light was applied near the site of electrical stimulation, via a flexible fibre optic. Paired applications of light produced increases in threshold that were reduced on the second application, the response recovering with increasing delays, with a time constant of 24 s. 3-min duration single applications of laser light gave rise to a rapid increase in threshold followed by a fade, whose time-constant was between 40 and 50 s. After-effects were sometimes apparent following the light application, where the resting threshold was reduced. The increase in threshold was partially blocked by 38.6 mM Li+ in combination with 5  µ M bumetanide, a manoeuvre increasing refractoriness and consistent with axonal depolarization. Assessing the effect of laser light on the nerve input resistance ruled out a previously suggested fall in myelin resistance as contributing to threshold changes. These data appear consistent with an axonal membrane potential that partly relies on temperature-dependent electroneutral Na+ influx, and where fade in the response to the laser may be caused by a gradually diminishing Na+ pump-induced hyperpolarization, in response to falling intracellular [Na+].


Assuntos
Axônios , Lasers , Nervo Óptico , Sódio , Animais , Ratos , Nervo Óptico/metabolismo , Sódio/metabolismo , Axônios/metabolismo , Axônios/fisiologia , Axônios/efeitos da radiação , Potenciais da Membrana/fisiologia , Masculino , Bumetanida/farmacologia , Ratos Sprague-Dawley
20.
Nanomaterials (Basel) ; 14(2)2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38251129

RESUMO

In recent nanomaterials research, combining nanoporous carbons with metallic nanoparticles, like palladium (Pd), has emerged as a focus due to their potential in energy, environmental and biomedical fields. This study presents a novel approach for synthesizing Pd-decorated carbons using magnetron sputter deposition. This method allows for the functionalization of nanoporous carbon surfaces with Pd nano-sized islands, creating metal-carbon nanocomposites through brief deposition times of up to 15 s. The present research utilized direct current magnetron sputtering to deposit Pd islands on a flexible activated carbon cloth substrate. The surface chemistry, microstructure, morphology and pore structure were analyzed using a variety of material characterization techniques, including X-ray photoelectron spectroscopy, X-ray diffraction, Raman spectroscopy, gas sorption analysis and scanning electron microscopy. The results showed Pd islands of varying sizes distributed across the cloth's carbon fibers, achieving high-purity surface modifications without the use of chemicals. The synthesis method preserves the nanoporous structure of the carbon cloth substrate while adding functional Pd islands, which could be potentially useful in emerging fields like hydrogen storage, fuel cells and biosensors. This approach demonstrates the possibility of creating high-quality metal-carbon composites using a simple, clean and economical method, expanding the possibilities for future nanomaterial-based applications.

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