RESUMO
Polarization of the plasma membrane (PM) into domains is an important mechanism to compartmentalize cellular activities and to establish cell polarity. Polarization requires formation of diffusion barriers that prevent mixing of proteins between domains. Recent studies have uncovered that the endoplasmic reticulum (ER) of budding yeast and neurons is polarized by diffusion barriers, which in neurons controls glutamate signaling in dendritic spines. The molecular identity of these barriers is currently unknown. Here, we show that a direct interaction between the ER protein Scs2 and the septin Shs1 creates the ER diffusion barrier in yeast. Barrier formation requires Epo1, a novel ER-associated subunit of the polarisome that interacts with Scs2 and Shs1. ER-septin tethering polarizes the ER into separate mother and bud domains, one function of which is to position the spindle in the mother until M phase by confining the spindle capture protein Num1 to the mother ER.
Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular/metabolismo , Retículo Endoplasmático/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Transporte/genética , Polaridade Celular , Proteínas do Citoesqueleto/metabolismo , Difusão , Retículo Endoplasmático/química , Proteínas de Membrana/genética , Membrana Nuclear/metabolismo , Fase S , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genéticaRESUMO
Cancer is a disease of aging and, as the world's population ages, the number of older persons with cancer is increasing and will make up a growing share of the oncology population in virtually every country. Despite this, older patients remain vastly underrepresented in research that sets the standards for cancer treatments. Consequently, most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients, and effective strategies to improve clinical trial participation of older adults with cancer remain sparse. For this systematic review, the authors evaluated published studies regarding barriers to participation and interventions to improve participation of older adults in cancer trials. The quality of the available evidence was low and, despite a literature describing multifaceted barriers, only one intervention study aimed to increase enrollment of older adults in trials. The findings starkly amplify the paucity of evidence-based, effective strategies to improve participation of this underrepresented population in cancer trials. Within these limitations, the authors provide their opinion on how the current cancer research infrastructure must be modified to accommodate the needs of older patients. Several underused solutions are offered to expand clinical trials to include older adults with cancer. However, as currently constructed, these recommendations alone will not solve the evidence gap in geriatric oncology, and efforts are needed to meet older and frail adults where they are by expanding clinical trials designed specifically for this population and leveraging real-world data.
Assuntos
Geriatria/estatística & dados numéricos , Oncologia/estatística & dados numéricos , Neoplasias/terapia , Participação do Paciente/psicologia , Seleção de Pacientes , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos como Assunto , Geriatria/métodos , Geriatria/tendências , Humanos , Oncologia/métodos , Oncologia/tendências , Neoplasias/diagnóstico , Participação do Paciente/estatística & dados numéricos , Estados UnidosRESUMO
BACKGROUND: Variant classification in the setting of germline genetic testing is necessary for patients and their families to receive proper care. Variants are classified as pathogenic (P), likely pathogenic (LP), uncertain significance (VUS), likely benign (LB) and benign (B) using the standards and guidelines recommended by the American College of Medical Genetics and the Association for Molecular Pathology, with modifications for specific genes. As the literature continues to rapidly expand, and evidence continues to accumulate, prior classifications can be updated accordingly. In this study, we aim to characterise variant reclassifications in Ontario. METHODS: DNA samples from patients seen at hereditary cancer clinics in Ontario from January 2012 to April 2022 were submitted for testing. Patients met provincial eligibility criteria for testing for hereditary cancer syndromes or polycystic kidney disease. Reclassification events were determined to be within their broader category of significance (B to LB or vice versa, or P to LP or vice versa) or outside of their broader category as significance (ie, significant reclassifications from B/LB or VUS or P/LP, from P/LP to VUS or B/LB, or from VUS to any other category). RESULTS: Of the 8075 unique variants included in this study, 23.7% (1912) of variants were reassessed, and 7.2% (578) of variants were reclassified. Of these, 351 (60.7%) variants were reclassified outside of their broader category of significance. Overall, the final classification was significantly different for 336 (58.1%) variants. Importantly, most reclassified variants were downgraded to a more benign classification (n=245; 72.9%). Of note, most reclassified VUS was downgraded to B/LB (n=233; 84.7%). CONCLUSIONS: The likelihood for reclassification of variants on reassessment is high. Most reclassified variants were downgraded to a more benign classification. Our findings highlight the importance of periodic variant reassessment to ensure timely and appropriate care for patients and their families.
Assuntos
Testes Genéticos , Variação Genética , Humanos , Testes Genéticos/métodos , Ontário/epidemiologia , Mutação em Linhagem Germinativa/genética , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/classificação , Feminino , Laboratórios Clínicos , Técnicas de Diagnóstico Molecular/métodosRESUMO
The potential-dependent negative fractional reaction orders with respect to the CO partial pressures were measured for CO2 electroreduction (CO2R) on Au under mass-transfer-controlled conditions using a rotating ring-disk electrode setup. At high overpotentials, the CO reaction order approaches -1 due to enhanced CO adsorption on Au, which is supported by kinetic analysis and density functional theory (DFT) simulations. This work illustrates that the CO site-blocking effect cannot be ignored, even on a weak CO-binding metal such as Au in the electrochemical environment. The CO site-blocking effect can greatly hamper the activity and the selectivity of the CO2R to CO. This observation enriches the current mechanistic understanding of the CO2R and could have significant implications not only in the theoretical modeling of the CO2R but also in the evaluation of intrinsic CO2R activity at practical current density and high conversion conditions.
RESUMO
BACKGROUND: Lower respiratory tract infections (LRTIs) in early childhood are known to influence lung development and lifelong lung health, but their link to premature adult death from respiratory disease is unclear. We aimed to estimate the association between early childhood LRTI and the risk and burden of premature adult mortality from respiratory disease. METHODS: This longitudinal observational cohort study used data collected prospectively by the Medical Research Council National Survey of Health and Development in a nationally representative cohort recruited at birth in March, 1946, in England, Scotland, and Wales. We evaluated the association between LRTI during early childhood (age <2 years) and death from respiratory disease from age 26 through 73 years. Early childhood LRTI occurrence was reported by parents or guardians. Cause and date of death were obtained from the National Health Service Central Register. Hazard ratios (HRs) and population attributable risk associated with early childhood LRTI were estimated using competing risks Cox proportional hazards models, adjusted for childhood socioeconomic position, childhood home overcrowding, birthweight, sex, and smoking at age 20-25 years. We compared mortality within the cohort studied with national mortality patterns and estimated corresponding excess deaths occurring nationally during the study period. FINDINGS: 5362 participants were enrolled in March, 1946, and 4032 (75%) continued participating in the study at age 20-25 years. 443 participants with incomplete data on early childhood (368 [9%] of 4032), smoking (57 [1%]), or mortality (18 [<1%]) were excluded. 3589 participants aged 26 years (1840 [51%] male and 1749 [49%] female) were included in the survival analyses from 1972 onwards. The maximum follow-up time was 47·9 years. Among 3589 participants, 913 (25%) who had an LRTI during early childhood were at greater risk of dying from respiratory disease by age 73 years than those with no LRTI during early childhood (HR 1·93, 95% CI 1·10-3·37; p=0·021), after adjustment for childhood socioeconomic position, childhood home overcrowding, birthweight, sex, and adult smoking. This finding corresponded to a population attributable risk of 20·4% (95% CI 3·8-29·8) and 179 188 (95% CI 33 806-261 519) excess deaths across England and Wales between 1972 and 2019. INTERPRETATION: In this prospective, life-spanning, nationally representative cohort study, LRTI during early childhood was associated with almost a two times increased risk of premature adult death from respiratory disease, and accounted for one-fifth of these deaths. FUNDING: National Institute for Health and Care Research Imperial Biomedical Research Centre, Royal Brompton and Harefield National Health Service (NHS) Foundation Trust, Royal Brompton and Harefield Hospitals Charity and Imperial College Healthcare NHS Trust, UK Medical Research Council.
Assuntos
Transtornos Respiratórios , Infecções Respiratórias , Recém-Nascido , Humanos , Masculino , Pré-Escolar , Adulto , Feminino , Adulto Jovem , Estudos de Coortes , Reino Unido/epidemiologia , Estudos Prospectivos , Peso ao Nascer , Medicina EstatalRESUMO
BACKGROUND: Consistent patterns of reduced cortical thickness have been identified in early Alzheimer's disease (AD). However, the pathological factors that influence rates of cortical thinning within these AD signature regions remain unclear. METHODS: Participants were from the Insight 46 substudy of the MRC National Survey of Health and Development (NSHD; 1946 British birth cohort), a prospective longitudinal cohort study. Linear regression was used to examine associations of baseline cerebral ß-amyloid (Aß) deposition, measured using florbetapir positron emission tomography, and baseline white matter hyperintensity volume (WMHV) on MRI, a marker of cerebral small vessel disease, with subsequent longitudinal changes in AD signature cortical thickness quantified from baseline and repeat MRI (mean [SD] interval 2.4 [0.2] years). RESULTS: In a population-based sample of 337 cognitively normal older white adults (mean [SD] age at baseline 70.5 [0.6] years; 48.1% female), higher global WMHV at baseline related to faster subsequent rates of cortical thinning in both AD signature regions (~0.15%/year faster per 10 mL additional WMHV), whereas baseline Aß status did not. Among Aß positive participants (n=56), there was some evidence that greater global Aß standardised uptake value ratio at baseline related to faster cortical thinning in the AD signature Mayo region, but this did not reach statistical significance (p=0.08). CONCLUSIONS: Cortical thinning within AD signature regions may develop via cerebrovascular pathways. Perhaps reflecting the age of the cohort and relatively low prevalence of Aß-positivity, robust Aß-related differences were not detected. Longitudinal follow-up incorporating additional biomarkers will allow assessment of how these relationships evolve closer to expected dementia onset.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Afinamento Cortical Cerebral , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Substância Branca , Humanos , Feminino , Masculino , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Estudos Longitudinais , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Afinamento Cortical Cerebral/diagnóstico por imagem , Afinamento Cortical Cerebral/patologia , Estudos Prospectivos , Etilenoglicóis , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Córtex Cerebral/metabolismo , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/patologia , Compostos de AnilinaRESUMO
Wild waterfowl serve as a reservoir of some astroviruses. Fecal samples from wild waterfowl collected at Hong Kong's Marshes were tested using pan-astrovirus reverse transcription-PCR. Positive samples underwent subsequent host identification using DNA barcoding. Based on deduced partial sequences, noteworthy samples from three astrovirus groups (mammalian, avian and unclassified astroviruses) were further analyzed by next-generation sequencing. One sample of Avastrovirus 4 clade, MP22-196, had a nearly complete genome identified. The results of ORF2 phylogenetic analysis and genetic distance analysis indicate that Avastrovirus 4 is classified as a distinct subclade within Avastrovirus. MP22-196 has typical astrovirus genome characteristics. The unique characteristics and potential differences of this genome, compared to other avian astrovirus sequences, involve the identification of a modified sgRNA sequence situated near the ORF2 start codon, which precedes the ORF1b stop codon. Additionally, the 3' UTR of MP22-196 is shorter than other avian astroviruses. This study expands our understanding of the Avastrovirus 4 clade.
Assuntos
Infecções por Astroviridae , Aves , Fezes , Variação Genética , Genoma Viral , Filogenia , Animais , Hong Kong , Aves/virologia , Fezes/virologia , Infecções por Astroviridae/veterinária , Infecções por Astroviridae/virologia , Animais Selvagens/virologia , Doenças das Aves/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Avastrovirus/genética , Avastrovirus/classificação , Avastrovirus/isolamento & purificação , RNA Viral/genética , Fases de Leitura Aberta , Astroviridae/genética , Astroviridae/isolamento & purificação , Astroviridae/classificaçãoRESUMO
BACKGROUND: Although age is the biggest known risk factor for dementia, there remains uncertainty about other factors over the life course that contribute to a person's risk for cognitive decline later in life. Furthermore, the pathological processes leading to dementia are not fully understood. The main goals of Insight 46-a multi-phase longitudinal observational study-are to collect detailed cognitive, neurological, physical, cardiovascular, and sensory data; to combine those data with genetic and life-course information collected from the MRC National Survey of Health and Development (NSHD; 1946 British birth cohort); and thereby contribute to a better understanding of healthy ageing and dementia. METHODS/DESIGN: Phase 1 of Insight 46 (2015-2018) involved the recruitment of 502 members of the NSHD (median age = 70.7 years; 49% female) and has been described in detail by Lane and Parker et al. 2017. The present paper describes phase 2 (2018-2021) and phase 3 (2021-ongoing). Of the 502 phase 1 study members who were invited to a phase 2 research visit, 413 were willing to return for a clinic visit in London and 29 participated in a remote research assessment due to COVID-19 restrictions. Phase 3 aims to recruit 250 study members who previously participated in both phases 1 and 2 of Insight 46 (providing a third data time point) and 500 additional members of the NSHD who have not previously participated in Insight 46. DISCUSSION: The NSHD is the oldest and longest continuously running British birth cohort. Members of the NSHD are now at a critical point in their lives for us to investigate successful ageing and key age-related brain morbidities. Data collected from Insight 46 have the potential to greatly contribute to and impact the field of healthy ageing and dementia by combining unique life course data with longitudinal multiparametric clinical, imaging, and biomarker measurements. Further protocol enhancements are planned, including in-home sleep measurements and the engagement of participants through remote online cognitive testing. Data collected are and will continue to be made available to the scientific community.
Assuntos
Demência , Idoso , Feminino , Humanos , Masculino , Envelhecimento , Assistência Ambulatorial , Encéfalo , Estudos Observacionais como AssuntoRESUMO
The arms race between bacteria and the phages that infect them drives the continual evolution of diverse anti-phage defences. Previously described anti-phage systems have highly varied defence mechanisms1-11; however, all mechanisms rely on protein components to mediate defence. Here we report a chemical anti-phage defence system that is widespread in Streptomyces. We show that three naturally produced molecules that insert into DNA are able to block phage replication, whereas molecules that target DNA by other mechanisms do not. Because double-stranded DNA phages are the most numerous group in the biosphere and the production of secondary metabolites by bacteria is ubiquitous12, this mechanism of anti-phage defence probably has a major evolutionary role in shaping bacterial communities.
Assuntos
Bacteriófagos/efeitos dos fármacos , Bacteriófagos/genética , Metabolismo Secundário , Streptomyces/química , Streptomyces/virologia , Replicação Viral/efeitos dos fármacos , Bacteriófago lambda/efeitos dos fármacos , Bacteriófago lambda/genética , Bacteriófago lambda/crescimento & desenvolvimento , Bacteriófago lambda/fisiologia , Bacteriófagos/crescimento & desenvolvimento , Evolução Biológica , DNA Viral/biossíntese , DNA Viral/genética , Daunorrubicina/farmacologia , Escherichia coli/virologia , Pseudomonas aeruginosa/virologia , Streptomyces/metabolismoRESUMO
OBJECTIVE: Chromosomal microarray (CMA), while considered the gold standard for detecting copy number variants (CNVs) in prenatal diagnostics, has its limitations, including the necessity to replace aging microarray equipment, low throughput, a static design, and an inefficient multi-day workflow. This study evaluates the feasibility of low-pass genome sequencing (LP-GS) as a potential replacement for CMA in prenatal diagnostics. METHODS: We comprehensively compared LP-GS at 10x and 5x average depths with CMA in a prenatal laboratory. We examined parameters, including concordance, sensitivity, specificity, workflow efficiency, and cost-effectiveness. RESULTS: We found a high degree of agreement between LP-GS and CMA for detecting CNVs and absence of heterozygosity. Furthermore, compared to CMA, LP-GS increased workflow efficiency and proved to be cost-neutral at 10x and cost-effective at 5x. CONCLUSION: Our study suggests that LP-GS is a promising alternative to CMA in prenatal diagnostics, offering advantages, including a more efficient workflow and scalability for larger testing volumes. Importantly, for clinical laboratories that have adopted next-generation sequencing in a separate capacity, LP-GS facilitates a unified NGS-centric approach, enabling workflow consolidation. By offering a single, streamlined platform for detecting a broad range of genetic variants, LP-GS may represent a critical step toward enhancing the diagnostic capabilities of prenatal laboratories.
Assuntos
Variações do Número de Cópias de DNA , Diagnóstico Pré-Natal , Gravidez , Feminino , Humanos , Mapeamento Cromossômico , Análise em MicrossériesRESUMO
BACKGROUND: It is known that many surgeons encounter intraoperative adverse events which can result in Second Victim Syndrome (SVS), with significant detriment to their emotional and physical health. There is, however, a paucity of Asian studies in this space. The present study thus aimed to explore the degree to which the experience of an adverse event is common among surgeons in Singapore, as well as its impact, and factors affecting their responses and perceived support systems. METHODS: A self-administered survey was sent to surgeons at four large tertiary hospitals. The 42-item questionnaire used a systematic closed and open approach, to assess: Personal experience with intraoperative adverse events, emotional, psychological and physical impact of these events and perceived support systems. RESULTS: The response rate was 57.5% (n = 196). Most respondents were male (54.8%), between 35 and 44 years old, and holding the senior consultant position. In the past 12 months alone, 68.9% recalled an adverse event. The emotional impact was significant, including sadness (63.1%), guilt (53.1%) and anxiety (45.4%). Speaking to colleagues was the most helpful support source (66.7%) and almost all surgeons did not receive counselling (93.3%), with the majority deeming it unnecessary (72.2%). Notably, 68.1% of the surgeons had positive takeaways, gaining new insight and improving vigilance towards errors. Both gender and surgeon experience did not affect the likelihood of errors and emotional impact, but more experienced surgeons were less likely to have positive takeaways (p = 0.035). Individuals may become advocates for patient safety, while simultaneously championing the cause of psychological support for others. CONCLUSIONS: Intraoperative adverse events are prevalent and its emotional impact is significant, regardless of the surgeon's experience or gender. While colleagues and peer discussions are a pillar of support, healthcare institutions should do more to address the impact and ensuing consequences.
Assuntos
Complicações Intraoperatórias , Cirurgiões , Humanos , Singapura , Estudos Transversais , Masculino , Feminino , Adulto , Cirurgiões/psicologia , Cirurgiões/estatística & dados numéricos , Inquéritos e Questionários , Complicações Intraoperatórias/epidemiologia , Pessoa de Meia-Idade , Erros Médicos/estatística & dados numéricos , Erros Médicos/psicologia , Emoções , Apoio SocialRESUMO
There are currently no disease-modifying treatments for Alzheimer's disease (AD), and an understanding of preclinical causal biomarkers to help target disease pathogenesis in the earliest phases remains elusive. Here, we investigated whether 19 metabolites previously associated with midlife cognition-a preclinical predictor of AD-translate to later clinical risk, using Mendelian randomization (MR) to tease out AD-specific causal relationships. Summary statistics from the largest genome-wide association studies (GWASs) for AD and metabolites were used to perform bidirectional univariable MR. Bayesian model averaging (BMA) was additionally performed to address high correlation between metabolites and identify metabolite combinations that may be on the AD causal pathway. Univariable MR indicated four extra-large high-density lipoproteins (XL.HDL) on the causal pathway to AD: free cholesterol (XL.HDL.FC: 95% CI = 0.78 to 0.94), total lipids (XL.HDL.L: 95% CI = 0.80 to 0.97), phospholipids (XL.HDL.PL: 95% CI = 0.81 to 0.97), and concentration of XL.HDL particles (95% CI = 0.79 to 0.96), significant at an adjusted P < 0.009. MR-BMA corroborated XL.HDL.FC to be among the top three causal metabolites, in addition to total cholesterol in XL.HDL (XL.HDL.C) and glycoprotein acetyls (GP). Both XL.HDL.C and GP demonstrated suggestive univariable evidence of causality (P < 0.05), and GP successfully replicated within an independent dataset. This study offers insight into the causal relationship between metabolites demonstrating association with midlife cognition and AD. It highlights GP in addition to several XL.HDLs-particularly XL.HDL.FC-as causal candidates warranting further investigation. As AD pathology is thought to develop decades prior to symptom onset, expanding on these findings could inform risk reduction strategies.
Assuntos
Doença de Alzheimer/genética , Sangue/metabolismo , Cognição/fisiologia , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/etiologia , Teorema de Bayes , Biomarcadores/sangue , Causalidade , Colesterol , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Biologia Computacional/métodos , Bases de Dados Genéticas , Predisposição Genética para Doença/genética , Variação Genética/genética , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana/métodos , Metabolômica/métodos , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Triglicerídeos/sangueRESUMO
Dysphagia is a well-documented sequela of stroke. Recent advancements in medical treatments for stroke include reperfusion therapies (endovascular thrombectomy (EVT) and thrombolysis). As outcomes following reperfusion therapies are typically measured via general functional scales, the pattern and progression of acute dysphagia following reperfusion therapies is less known. To determine the progression of acute dysphagia (0-72 h) following reperfusion therapies and relationships between various stroke parameters and dysphagia, twenty-six patients were prospectively recruited across two EVT and thrombolysis centres in Brisbane, Australia. Dysphagia was screened via the Gugging Swallowing Screen (GUSS) at the bedside at three timepoints: 0-24 h, 24-48 h, and 48-72 h post-reperfusion therapies. Across three groups (EVT only, thrombolysis only, or both), the incidence of any dysphagia within the first 24 h of reperfusion therapy was 92.31% (n = 24/26), 91.30% (n = 21/23) by 48 h, and 90.91% (n = 20/22) by 72 h. Fifteen patients presented with severe dysphagia at 0-24 h, 10 at 24-48 h, and 10 at 48-72 h. Whilst dysphagia was not significantly correlated to infarct penumbra/core size, dysphagia severity was significantly related to the number of passes required during EVT (p = 0.009).Dysphagia continues to persist in the acute stroke population despite recent advancements in technology aimed to reduce morbidity and mortality post-stroke. Further research is required to establish protocols for management of dysphagia post-reperfusion therapies.
Assuntos
Isquemia Encefálica , Transtornos de Deglutição , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Isquemia Encefálica/terapia , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Estudos Prospectivos , Projetos Piloto , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Reperfusão/efeitos adversos , Resultado do TratamentoRESUMO
Dysphagia and chronic aspiration are common post-irradiation complications in nasopharyngeal carcinoma (NPC) survivors. Expiratory Muscle Strength Training (EMST) is a simple device-driven exercise therapy for swallowing training. This study investigates the effectiveness of EMST in a group of post-irradiated NPC patients. This prospective cohort, including twelve patients with previous irradiation for NPC and with swallowing disturbance, was performed between 2019 and 2021 in a single institution. Patients were trained with EMST for 8 weeks. Non-parametric analyses examined effects of EMST on primary outcome, maximum expiratory pressure. Secondary outcomes were measured with Penetration-aspiration scale, Yale pharyngeal residue severity rating scale (YPRSRS) by flexible endoscopic evaluation of swallowing, and Eating Assessment Tool (EAT-10) and M.D. Anderson Dysphagia Inventory questionnaire. Twelve patients, with a mean (SD) age of 64.3 (8.2) were recruited. There was no patient dropout with 88.9% overall compliance of training. Maximum expiratory pressure improved by 41% (median 94.5 to 133.5 cmH2O, p = 0.003). There was reduction in Penetration-aspiration scale with thin liquid (median 4 to 3, p = 0.026), and in YPRSRS at pyriform fossa with mildly thick liquid (p = 0.021) and at vallecula with thin liquid (p = 0.034), mildly thick liquid (p = 0.014) and pureed meat congee (p = 0.016). Questionnaire scores did not significantly change statistically. EMST is an easy-to-use and effective exercise therapy to improve airway safety and swallowing function in post-irradiated NPC survivors.
Assuntos
Transtornos de Deglutição , Neoplasias Nasofaríngeas , Treinamento Resistido , Humanos , Deglutição/fisiologia , Carcinoma Nasofaríngeo/radioterapia , Estudos Prospectivos , Aspiração Respiratória , Neoplasias Nasofaríngeas/complicações , Neoplasias Nasofaríngeas/radioterapia , Músculos , Força Muscular/fisiologiaRESUMO
MXenes and sulfurized polyacrylonitrile (S-PAN) are emerging as possible contenders to resolve the polysulfide dissolution and volumetric expansion issues in sodium-sulfur batteries. Herein, we explore the interactions between Ti3C2Tx MXenes and S-PAN with traditional binders such as polyvinylidene difluoride (PVDF), poly(acrylic acid) (PAA), and carboxymethyl cellulose (CMC) in Na-S batteries for the first time. We hypothesize that the linearity and polarity of the binder significantly influence the dispersion of S-PAN over Ti3C2Tx. The three-dimensional polar CMC binder resulted in better contact surface area with both S-PAN and Ti3C2Tx. Moreover, the improved binding of the discharge products with the CMC binder effectively traps them and prevents unwanted shuttling. Consequently, the Na-S battery using the CMC binder displayed a high initial capacity of 1282 mAh/g(s) at 0.2 C and a low capacity fading of 0.092% per cycle over 300 cycles. This work highlights the importance of understanding MXene-binder interactions in sulfur cathodes.
RESUMO
Powdery hexagonal boron nitride (h-BN), as an important material for electrochemical energy storage, has been typically synthesized in bulk and one/two-dimensional (1/2D) nanostructured morphologies. However, until now, no method has been developed to synthesize powdery three-dimensional (3D) h-BN. This work introduces a novel NaCl-glucose-assisted strategy to synthesize micron-sized 3D h-BN with a honeycomb-like structure and its proposed formation mechanism. We propose that NaCl acts as the template of 3D structure and promotes the nitridation reaction by adsorbing NH3 . Glucose facilitates the homogeneous coating of boric acid onto the NaCl surface via functionalizing the NaCl surface. During the nitridation reaction, boron oxides (BO4 and BO3 ) form from a dehydration reaction of boric acid, which is then reduced to O2 -B-N and O-B-N2 intermediates before finally being reduced to BN3 by NH3 . When incorporated into polyethylene oxide-based electrolytes for Li metal batteries, 5â wt % of 3D h-BN significantly enhances ionic conductivity and mechanical strength. Consequently, this composite electrolyte demonstrates superior electrochemical stability. It delivers 300â h of stable cycles in the Li//Li cell at 0.1â mA cm-2 and retains 89 % of discharge capacity (138.9â mAh g-1 ) after 100 cycles at 1â C in the LFP//Li full cell.
RESUMO
BACKGROUND: Endovascular thrombectomy (EVT) access in remote areas is limited. Preliminary data suggest that long distance transfers for EVT may be beneficial; however, the magnitude and best imaging strategy at the referring center remains uncertain. We hypothesized that patients transferred >300 miles would benefit from EVT, achieving rates of functional independence (modified Rankin Scale [mRS] score of 0-2) at 3 months similar to those patients treated at the comprehensive stroke center in the randomized EVT extended window trials and that the selection of patients with computed tomography perfusion (CTP) at the referring site would be associated with ordinal shift toward better outcomes on the mRS. METHODS: This is a retrospective analysis of patients transferred from 31 referring hospitals >300 miles (measured by the most direct road distance) to 9 comprehensive stroke centers in Australia and New Zealand for EVT consideration (April 2016 through May 2021). RESULTS: There were 131 patients; the median age was 64 [53-74] years and the median baseline National Institutes of Health Stroke Scale score was 16 [12-22]. At baseline, 79 patients (60.3%) had noncontrast CT+CT angiography, 52 (39.7%) also had CTP. At the comprehensive stroke center, 114 (87%) patients underwent cerebral angiography, and 96 (73.3%) proceeded to EVT. At 3 months, 62 patients (48.4%) had an mRS score of 0 to 2 and 81 (63.3%) mRS score of 0 to 3. CTP selection at the referring site was not associated with better ordinal scores on the mRS at 3 months (mRS median of 2 [1-3] versus 3 [1-6] in the patients selected with noncontrast CT+CT angiography, P=0.1). Nevertheless, patients selected with CTP were less likely to have an mRS score of 5 to 6 (odds ratio 0.03 [0.01-0.19]; P<0.01). CONCLUSIONS: In selected patients transferred >300 miles, there was a benefit for EVT, with outcomes similar to those treated in the comprehensive stroke center in the EVT extended window trials. Remote hospital CTP selection was not associated with ordinal mRS improvement, but was associated with fewer very poor 3-month outcomes.
Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Pessoa de Meia-Idade , Isquemia Encefálica/terapia , Estudos Retrospectivos , Nova Zelândia , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Procedimentos Endovasculares/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Ketone bodies (KBs) are an alternative energy supply for brain functions when glucose is limited. The most abundant ketone metabolite, 3-ß-hydroxybutyrate (BOHBUT), has been suggested to prevent or delay cognitive impairment, but the evidence remains unclear. We triangulated observational and Mendelian randomization (MR) studies to investigate the association and causation between KBs and cognitive function. METHODS: In observational analyses of 5506 participants aged ≥ 45 years from the Whitehall II study, we used multiple linear regression to investigate the associations between categorized KBs and cognitive function scores. Two-sample MR was carried out using summary statistics from an in-house KBs meta-analysis between the University College London-London School of Hygiene and Tropical Medicine-Edinburgh-Bristol (UCLEB) Consortium and Kettunen et al. (N = 45,031), and publicly available summary statistics of cognitive performance and Alzheimer's disease (AD) from the Social Science Genetic Association Consortium (N = 257,841), and the International Genomics of Alzheimer's Project (N = 54,162), respectively. Both strong (P < 5 × 10-8) and suggestive (P < 1 × 10-5) sets of instrumental variables for BOHBUT were applied. Finally, we performed cis-MR on OXCT1, a well-known gene for KB catabolism. RESULTS: BOHBUT was positively associated with general cognitive function (ß = 0.26, P = 9.74 × 10-3). In MR analyses, we observed a protective effect of BOHBUT on cognitive performance (inverse variance weighted: ßIVW = 7.89 × 10-2, PIVW = 1.03 × 10-2; weighted median: ßW-Median = 8.65 × 10-2, PW-Median = 9.60 × 10-3) and a protective effect on AD (ßIVW = - 0.31, odds ratio: OR = 0.74, PIVW = 3.06 × 10-2). Cis-MR showed little evidence of therapeutic modulation of OXCT1 on cognitive impairment. CONCLUSIONS: Triangulation of evidence suggests that BOHBUT has a beneficial effect on cognitive performance. Our findings raise the hypothesis that increased BOHBUT may improve general cognitive functions, delaying cognitive impairment and reducing the risk of AD.
Assuntos
Doença de Alzheimer , Corpos Cetônicos , Humanos , Ácido 3-Hidroxibutírico , Doença de Alzheimer/genética , Cognição , Cetonas , Análise da Randomização Mendeliana , Pessoa de Meia-IdadeRESUMO
Optimizing catalysts for competitive photocatalytic reactions demand individually tailored band structure as well as intertwined interactions of light absorption, reaction activity, mass, and charge transport. Here, a nanoparticulate host-guest structure is rationally designed that can exclusively fulfil and ideally control the aforestated uncompromising requisites for catalytic reactions. The all-inclusive model catalyst consists of porous Co3 O4 host and Znx Cd1- x S guest with controllable physicochemical properties enabled by self-assembled hybrid structure and continuously amenable band gap. The effective porous topology nanoassembly, both at the exterior and the interior pores of a porous metal-organic framework (MOF), maximizes spatially immobilized semiconductor nanoparticles toward high utilization of particulate heterojunctions for vital charge and reactant transfer. In conjunction, the zinc constituent band engineering is found to regulate the light/molecules absorption, band structure, and specific reaction intermediates energy to attain high photocatalytic CO2 reduction selectivity. The optimal catalyst exhibits a H2 -generation rate up to 6720 µmol g-1 h-1 and a CO production rate of 19.3 µmol g-1 h-1 . These findings provide insight into the design of discrete host-guest MOF-semiconductor hybrid system with readily modulated band structures and well-constructed heterojunctions for selective solar-to-chemical conversion.
RESUMO
BACKGROUND: Percentage excess weight loss (%EWL) and percentage total weight loss (%TWL) are used for reporting outcomes after bariatric surgery. However, they are not ideal for comparing outcomes on populations of varied initial body mass index (BMI). This study aimed to validate a recently introduced metric - percentage alterable weight loss (%AWL), after laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (LRYGB). METHODS: Analysis of weight data of all patients who had undergone LSG and LRYGB until the end of the year 2021. Outcomes for both procedures were analyzed separately. The patients were divided into quartile subgroups Q1 (lowest BMI) to Q4 (highest BMI) and weight loss up to 5 years postoperatively was compared using %EWL, %TWL and %AWL metrics. An intermediary metric was also tested for its effect on the weight loss patterns for both procedures. RESULTS: The cohort included 1020 LSG and 322 LRYGB patients, with initial mean BMI of 43.5 ± 7.5 and 41.9 ± 8.3 kg/m2, respectively. %EWL significantly favors lower BMI subgroups for both procedures. %TWL is ideal for comparing weight loss during the first 6 months but it then favors higher BMI subgroups beyond 6 months. %AWL with reference BMI of 13 kg/m2 seems the best metric for medium-term comparison of weight loss for LRYGB and an intermediary metric based on BMI 8 kg/m2 provides the best fit for medium-term comparison for LSG. CONCLUSIONS: %TWL is least influenced by initial BMI during short-term follow-up after LSG and LRYGB. For medium-term comparison, %AWL is best suited for LRYGB while an intermediary metric is found to provide the best fit for LSG.