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1.
Nature ; 629(8013): 769-772, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38778233

RESUMEN

The magnetic dynamo cycle of the Sun features a distinct pattern: a propagating region of sunspot emergence appears around 30° latitude and vanishes near the equator every 11 years (ref. 1). Moreover, longitudinal flows called torsional oscillations closely shadow sunspot migration, undoubtedly sharing a common cause2. Contrary to theories suggesting deep origins of these phenomena, helioseismology pinpoints low-latitude torsional oscillations to the outer 5-10% of the Sun, the near-surface shear layer3,4. Within this zone, inwardly increasing differential rotation coupled with a poloidal magnetic field strongly implicates the magneto-rotational instability5,6, prominent in accretion-disk theory and observed in laboratory experiments7. Together, these two facts prompt the general question: whether the solar dynamo is possibly a near-surface instability. Here we report strong affirmative evidence in stark contrast to traditional models8 focusing on the deeper tachocline. Simple analytic estimates show that the near-surface magneto-rotational instability better explains the spatiotemporal scales of the torsional oscillations and inferred subsurface magnetic field amplitudes9. State-of-the-art numerical simulations corroborate these estimates and reproduce hemispherical magnetic current helicity laws10. The dynamo resulting from a well-understood near-surface phenomenon improves prospects for accurate predictions of full magnetic cycles and space weather, affecting the electromagnetic infrastructure of Earth.

2.
Nature ; 625(7994): 259-263, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38200302

RESUMEN

To run large-scale algorithms on a quantum computer, error-correcting codes must be able to perform a fundamental set of operations, called logic gates, while isolating the encoded information from noise1-8. We can complete a universal set of logic gates by producing special resources called magic states9-11. It is therefore important to produce high-fidelity magic states to conduct algorithms while introducing a minimal amount of noise to the computation. Here we propose and implement a scheme to prepare a magic state on a superconducting qubit array using error correction. We find that our scheme produces better magic states than those that can be prepared using the individual qubits of the device. This demonstrates a fundamental principle of fault-tolerant quantum computing12, namely, that we can use error correction to improve the quality of logic gates with noisy qubits. Moreover, we show that the yield of magic states can be increased using adaptive circuits, in which the circuit elements are changed depending on the outcome of mid-circuit measurements. This demonstrates an essential capability needed for many error-correction subroutines. We believe that our prototype will be invaluable in the future as it can reduce the number of physical qubits needed to produce high-fidelity magic states in large-scale quantum-computing architectures.

3.
Cereb Cortex ; 34(1)2024 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-37943770

RESUMEN

Empathic function, which is primarily manifested by facial imitation, is believed to play a pivotal role in interpersonal emotion regulation for mood reinstatement. To explore this association and its neural substrates, we performed a questionnaire survey (study l) to identify the relationship between empathy and interpersonal emotion regulation; and a task-mode fMRI study (study 2) to explore how facial imitation, as a fundamental component of empathic processes, promotes the interpersonal emotion regulation effect. Study 1 showed that affective empathy was positively correlated with interpersonal emotion regulation. Study 2 showed smaller negative emotions in facial imitation interpersonal emotion regulation (subjects imitated experimenter's smile while followed the interpersonal emotion regulation guidance) than in normal interpersonal emotion regulation (subjects followed the interpersonal emotion regulation guidance) and Watch conditions. Mirror neural system (e.g. inferior frontal gyrus and inferior parietal lobe) and empathy network exhibited greater activations in facial imitation interpersonal emotion regulation compared with normal interpersonal emotion regulation condition. Moreover, facial imitation interpersonal emotion regulation compared with normal interpersonal emotion regulation exhibited increased functional coupling from mirror neural system to empathic and affective networks during interpersonal emotion regulation. Furthermore, the connectivity of the right orbital inferior frontal gyrus-rolandic operculum lobe mediated the association between the accuracy of facial imitation and the interpersonal emotion regulation effect. These results show that the interpersonal emotion regulation effect can be enhanced by the target's facial imitation through increased functional coupling from mirror neural system to empathic and affective neural networks.


Asunto(s)
Regulación Emocional , Humanos , Mapeo Encefálico/métodos , Conducta Imitativa/fisiología , Imagen por Resonancia Magnética/métodos , Empatía , Neuroimagen Funcional , Emociones/fisiología , Expresión Facial
4.
Proc Natl Acad Sci U S A ; 119(30): e2206588119, 2022 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-35867821

RESUMEN

Oncogenic mutations within the epidermal growth factor receptor (EGFR) are found in 15 to 30% of all non-small-cell lung carcinomas. The term exon 19 deletion (ex19del) is collectively used to refer to more than 20 distinct genomic alterations within exon 19 that comprise the most common EGFR mutation subtype in lung cancer. Despite this heterogeneity, clinical treatment decisions are made irrespective of which EGFR ex19del variant is present within the tumor, and there is a paucity of information regarding how individual ex19del variants influence protein structure and function. Herein, we identified allele-specific functional differences among ex19del variants attributable to recurring sequence and structure motifs. We built all-atom structural models of 60 ex19del variants identified in patients and combined molecular dynamics simulations with biochemical and biophysical experiments to analyze three ex19del mutations (E746_A750, E746_S752 > V, and L747_A750 > P). We demonstrate that sequence variation in ex19del alters oncogenic cell growth, dimerization propensity, enzyme kinetics, and tyrosine kinase inhibitor (TKI) sensitivity. We show that in contrast to E746_A750 and E746_S752 > V, the L747_A750 > P variant forms highly active ligand-independent dimers. Enzyme kinetic analysis and TKI inhibition experiments suggest that E746_S752 > V and L747_A750 > P display reduced TKI sensitivity due to decreased adenosine 5'-triphosphate Km. Through these analyses, we propose an expanded framework for interpreting ex19del variants and considerations for therapeutic intervention.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Exones , Neoplasias Pulmonares , Alelos , Secuencias de Aminoácidos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Activación Enzimática/genética , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/química , Receptores ErbB/genética , Exones/genética , Humanos , Cinética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Recurrencia Local de Neoplasia/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Eliminación de Secuencia
5.
Neuroimage ; : 120789, 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39159702

RESUMEN

Interpersonal emotion regulation (IER) is a crucial ability for effectively recovering from negative emotions through social interaction. It has been emphasized that the empathy network, cognitive control network, and affective generation network sustain the deployment of IER. However, the temporal dynamics of functional connectivity among these networks of IER remains unclear. This study utilized IER task-fMRI and sliding window approach to examine both the stationary and dynamic functional connectivity (dFC) of IER. Fifty-five healthy participants were recruited for the present study. Through clustering analysis, four distinct brain states were identified in dFC. State 1 demonstrated situation modification stage of IER, with strong connectivity between affective generation and visual networks. State 2 exhibited pronounced connectivity between empathy network and both cognitive control and affective generation networks, reflecting the empathy stage of IER. Next, a 'top-down' pattern is observed between the connectivity of cognitive control and affective generation networks during the cognitive control stage of state 3. The affective response modulation stage of state 4 mainly involved connections between empathy and affective generation networks. Specifically, the degree centrality of the left middle temporal gyrus (MTG) mediated the association between one's IER tendency and the regulatory effects in state 2. The betweenness centrality of the left ventrolateral prefrontal cortex (VLPFC) mediated the association between one's IER efficiency and the regulatory effects in state 3. Altogether, these findings revealed that dynamic connectivity transitions among empathy, cognitive control, and affective generation networks, with the left VLPFC and MTG playing dominant roles, evident across the IER processing.

6.
Plant Cell ; 33(2): 290-305, 2021 04 17.
Artículo en Inglés | MEDLINE | ID: mdl-33793769

RESUMEN

Plants can contain biosynthetic gene clusters (BGCs) that nominally resemble those found in microbes. However, while horizontal gene transmission is often observed in microbes, plants are limited to vertical gene transmission, implying that their BGCs may exhibit distinct inheritance patterns. Rice (Oryza sativa) contains two unlinked BGCs involved in diterpenoid phytoalexin metabolism, with one clearly required for momilactone biosynthesis, while the other is associated with production of phytocassanes. Here, in the process of elucidating momilactone biosynthesis, genetic evidence was found demonstrating a role for a cytochrome P450 (CYP) from the other "phytocassane" BGC. This CYP76M8 acts after the CYP99A2/3 from the "momilactone" BGC, producing a hemiacetal intermediate that is oxidized to the eponymous lactone by a short-chain alcohol dehydrogenase also from this BGC. Thus, the "momilactone" BGC is not only incomplete, but also fractured by the need for CYP76M8 to act in between steps catalyzed by enzymes from this BGC. Moreover, as supported by similar activity observed with orthologs from the momilactone-producing wild-rice species Oryza punctata, the presence of CYP76M8 in the other "phytocassane" BGC indicates interdependent evolution of these two BGCs, highlighting the distinct nature of BGC assembly in plants.


Asunto(s)
Evolución Biológica , Vías Biosintéticas/genética , Diterpenos/metabolismo , Familia de Multigenes , Oryza/genética , Diterpenos/química , Regulación de la Expresión Génica de las Plantas , Oxidación-Reducción , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
7.
Psychol Med ; 54(4): 639-651, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37997708

RESUMEN

Reward processing dysfunctions are considered a candidate mechanism underlying anhedonia and apathy in depression. Neuroimaging studies have documented that neurofunctional alterations in mesocorticolimbic circuits may neurally mediate these dysfunctions. However, common and distinct neurofunctional alterations during motivational and hedonic evaluation of monetary and natural rewards in depression have not been systematically examined. Here, we capitalized on pre-registered neuroimaging meta-analyses to (1) establish general reward-related neural alterations in depression, (2) determine common and distinct alterations during the receipt and anticipation of monetary v. natural rewards, and, (3) characterize the differences on the behavioral, network, and molecular level. The pre-registered meta-analysis (https://osf.io/ay3r9) included 633 depressed patients and 644 healthy controls and revealed generally decreased subgenual anterior cingulate cortex and striatal reactivity toward rewards in depression. Subsequent comparative analyses indicated that monetary rewards led to decreased hedonic reactivity in the right ventral caudate while natural rewards led to decreased reactivity in the bilateral putamen in depressed individuals. These regions exhibited distinguishable profiles on the behavioral, network, and molecular level. Further analyses demonstrated that the right thalamus and left putamen showed decreased activation during the anticipation of monetary reward. The present results indicate that distinguishable neurofunctional alterations may neurally mediate reward-processing alterations in depression, in particular, with respect to monetary and natural rewards. Given that natural rewards prevail in everyday life, our findings suggest that reward-type specific interventions are warranted and challenge the generalizability of experimental tasks employing monetary incentives to capture reward dysregulations in everyday life.


Asunto(s)
Depresión , Motivación , Humanos , Depresión/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Neuroimagen , Recompensa , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología
8.
Artículo en Inglés | MEDLINE | ID: mdl-38886184

RESUMEN

BACKGROUND: Accumulating evidence shows that peri-conceptional and in-utero exposures have lifetime health impacts for mothers and their offspring. OBJECTIVES: We conducted a Follow-Up Study of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial with two objectives. First, we determined if women who enrolled at the Utah site (N = 1001) of the EAGeR trial (2007-2011, N = 1228) could successfully be contacted and agree to complete an online questionnaire on their reproductive, cardio-metabolic, and offspring respiratory health 9-14 years after original enrollment. Second, we evaluated if maternal exposure to low-dose aspirin (LDA) during pregnancy was associated with maternal cardio-metabolic health and offspring respiratory health. METHODS: The original EAGeR study population included women, 18-40 years of age, who had 1-2 prior pregnancy losses, and who were trying to become pregnant. At follow-up (2020-2021), participants from the Utah cohort completed a 13-item online questionnaire on reproductive and cardio-metabolic health, and those who had a live birth during EAGeR additionally completed a 7-item questionnaire on the index child's respiratory health. Primary maternal outcomes included hypertension and hypercholesterolemia; primary offspring outcomes included wheezing and asthma. RESULTS: Sixty-eight percent (n = 678) of participants enrolled in the follow-up study, with 10% and 15% reporting maternal hypertension and hypercholesterolemia, respectively; and 18% and 10% reporting offspring wheezing and asthma. We found no association between maternal LDA exposure and hypertension (risk difference [RD] -0.001, 95% confidence interval [CI] -0.05, 0.04) or hypercholesterolemia (RD -0.01, 95% CI -0.06, 0.05) at 9-14 years follow-up. Maternal LDA exposure was not associated with offspring wheezing (RD -0.002, 95% CI -0.08, 0.08) or asthma (RD 0.13, 95% CI 0.11, 0.37) at follow-up. Findings remained robust after considering potential confounding and selection bias. CONCLUSIONS: We observed no association between LDA exposure during pregnancy and maternal cardiometabolic or offspring respiratory health.

9.
Cereb Cortex ; 33(22): 11060-11069, 2023 11 04.
Artículo en Inglés | MEDLINE | ID: mdl-37771046

RESUMEN

Similarities between twins have been widely demonstrated, underscoring the remarkable influence of genetics across numerous traits. In this study, we explore the genetic underpinnings of the human brain by examining MRI data from the Queensland Twin Imaging study. Specifically, this study seeks to compare brain structure and function between twins and unrelated subjects, with an emphasis on describing the effects of genetic factors. To achieve these goals, we employed the source-based morphometry method to extract intrinsic components and elucidate recognizable patterns. Our results show that twins exhibit a higher degree of similarity in gray and white matter density compared with unrelated individuals. In addition, four distinct states of brain activity were identified using coactivation patterns analysis. Furthermore, twins demonstrated a greater degree of similarity in the temporal and spatial features of each state compared with unrelated subjects. Taken together, these results support the hypothesis that twins show greater similarity in both brain structure and dynamic functional brain activity. Further exploration of these methods may advance our understanding of the complex interplay between genes, environment, and brain networks.


Asunto(s)
Imagen por Resonancia Magnética , Sustancia Blanca , Humanos , Imagen por Resonancia Magnética/métodos , Gemelos/genética , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Cabeza , Gemelos Monocigóticos , Gemelos Dicigóticos
10.
Cereb Cortex ; 33(5): 1726-1738, 2023 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-35511500

RESUMEN

In this study, we examined structural and functional profiles of the insular cortex and mapped associations with well-described functional networks throughout the brain using diffusion tensor imaging (DTI) and resting-state functional connectivity (RSFC) data. We used a data-driven method to independently estimate the structural-functional connectivity of the insular cortex. Data were obtained from the Human Connectome Project comprising 108 adult participants. Overall, we observed moderate to high associations between the structural and functional mapping scores of 3 different insular subregions: the posterior insula (associated with the sensorimotor network: RSFC, DTI = 50% and 72%, respectively), dorsal anterior insula (associated with ventral attention: RSFC, DTI = 83% and 83%, respectively), and ventral anterior insula (associated with the frontoparietal: RSFC, DTI = 42% and 89%, respectively). Further analyses utilized meta-analytic decoding maps to demonstrate specific cognitive and affective as well as gene expression profiles of the 3 subregions reflecting the core properties of the insular cortex. In summary, given the central role of the insular in the human brain, our results revealing correspondence between DTI and RSFC mappings provide a complementary approach and insight for clinical researchers to identify dysfunctional brain organization in various neurological disorders associated with insular pathology.


Asunto(s)
Corteza Cerebral , Conectoma , Adulto , Humanos , Corteza Insular , Imagen de Difusión Tensora , Encéfalo , Mapeo Encefálico/métodos , Imagen por Resonancia Magnética
11.
World J Surg ; 48(5): 1037-1044, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38497974

RESUMEN

BACKGROUND: American Indian and Alaska Native (AIAN) health issues are understudied despite documentation of lower-than-average life expectancy. Urgent surgery is associated with higher rates of postsurgical complications and postoperative death. We assess whether American Indian and Alaska Native (AIAN) patients in Washington State are at greater risk of requiring urgent rather than elective surgery compared with non-Hispanic Whites (NHW). METHODS: We accessed data for the period 2009-2014 from the Washington State Comprehensive Hospital Abstract Reporting System (CHARS) database, which captures all statewide hospital admissions, to examine three common surgeries that are performed both urgently and electively: hip replacements, aortic valve replacements, and spinal fusions. We extracted patient race, age, insurance status, comorbidity, admission type, and procedures performed. We then constructed multivariable logistic regression models to identify factors associated with use of urgent surgical care. RESULTS: AIAN patients had lower mean age at surgery for all three surgeries compared with NHW patients. AIAN patients were at higher risk for urgent surgery for hip replacements (OR = 1.49, 95% CI 1.19-1.88), spinal fusions (OR = 1.39, 95% CI 1.04-1.87), and aortic valve replacements (OR = 2.06, 95% CI 1.12-3.80). CONCLUSION: AIAN patients were more likely to undergo urgent hip replacement, spinal fusion, and aortic valve replacement than NHW patients. AIAN patients underwent urgent surgery at younger ages. Medicaid insurance conferred higher risks for urgent surgery across all surgeries studied. Further research is warranted to more clearly identify the factors contributing to disparities among AIAN patients undergoing urgent surgery.


Asunto(s)
Procedimientos Quirúrgicos Electivos , Disparidades en Atención de Salud , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Artroplastia de Reemplazo de Cadera/estadística & datos numéricos , Procedimientos Quirúrgicos Electivos/estadística & datos numéricos , Disparidades en Atención de Salud/estadística & datos numéricos , Disparidades en Atención de Salud/etnología , Implantación de Prótesis de Válvulas Cardíacas/estadística & datos numéricos , Estudios Retrospectivos , Fusión Vertebral/estadística & datos numéricos , Washingtón , Indio Americano o Nativo de Alaska/estadística & datos numéricos
12.
Health Expect ; 27(1): e13982, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-39102699

RESUMEN

INTRODUCTION: Remote (digital and/or telephone) access and consultation models are being driven by national policy with the goal being that the National Health Service operate on a remote-first (digital-first) basis by 2029. Previous research has suggested that remote methods of access to care and consulting may act to widen health inequalities for certain patients and/or groups such as those from ethnic minorities. South Asian (SA) patients comprise the largest ethnic minority group in England. Understanding the experiences and needs of this group is critical to ensuring that general practice can deliver equitable, quality health care. METHODS: Qualitative study. 37 participants (from Indian, Pakistani and/or Bangladeshi background) were recruited to take part in either in-person preferred language focus groups or remote semistructured interviews in the English language. Thematic analysis was conducted to identify themes in the qualitative data. FINDINGS: Three major interlinked themes were identified: (1) reduced access, (2) reduced patient choice and (3) quality and safety concerns. The findings highlight access issues split by (i) general issues with appointment access via any remote means and (ii) specific issues related to language barriers creating additional barriers to access and care. Some patients valued the convenience of remote access but also raised concerns regarding appointment availability and reduced patient choice. Face-to-face consultations were preferable but less available. The findings underscore how participants perceived remote care to be of lesser quality and less safe. Concerns were greatest for those with limited English proficiency (LEP), with the removal of non-verbal aspects of communication and 'hands-on' care leading to perceptions of reduced psycho-social safety. CONCLUSION: SA patients' experiences of remote-led primary care access and care delivery were negative with only a minority viewing it positively and for certain limited scenarios. Face-to-face models of care remain the preferred mode of consultation, particularly for those with LEP. Hybrid models of access offer patients the greatest choice, and are likely to meet the varying needs of the South-Asian patient population going forwards. The remote first approach to primary care may be achievable as a service ideal, but its limitations need to be recognised and accounted for to ensure that primary care can be an equitable service, both now and in the future. PUBLIC CONTRIBUTION: Members of the public were involved in all phases of research in the study. This included co-working in partnership throughout the study including, reviewing patient-facing documents, recruiting participants, data facilitation, translation work, interpretation of the data and co-authors on this manuscript. The key to the success of our study was collaborative teamwork, which involved experienced members of the public with SA cultural knowledge working together with and integral to the research team for all components.


Asunto(s)
COVID-19 , Accesibilidad a los Servicios de Salud , Prioridad del Paciente , Atención Primaria de Salud , Investigación Cualitativa , Humanos , Inglaterra , COVID-19/etnología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Grupos Focales , Pueblo Asiatico , Barreras de Comunicación , Anciano , SARS-CoV-2 , Pakistán/etnología , Bangladesh/etnología , Entrevistas como Asunto
13.
J Minim Invasive Gynecol ; 31(7): 607-612, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38697259

RESUMEN

OBJECTIVE: To compare demographic characteristics of women with and without a diagnosis of endometriosis. DESIGN: Data were collected from the National Survey of Family Growth-a publicly available survey designed and administered by the Centers for Disease Control, which uses a nationally-representative sample of the United States population. Univariate data were reported as survey-weighted percentages and means and were analyzed using chi-square, t tests, and logistic regression. Analyses accounted for complex survey design. SETTING: United States. PARTICIPANTS: Interviews were conducted with 6141 female respondents, aged 15 to 50, between 2017 and 2019. INTERVENTIONS: Data were collected through in-person interviews. RESULTS: Nationally, 5.7% reported a diagnosis of endometriosis (95% CI 4.6-6.9%). Those with endometriosis were older, with a mean age of 39 (95% CI 38.1-39.9), compared to 31.7 (95% CI 31.2-32.2) among those without (p <.0005). Endometriosis diagnosis was significantly associated with race. Compared to non-Hispanic White women, Hispanic women had an adjusted odds ratio (aOR) of 0.37 (95% CI 0.21-0.65) for diagnosis of endometriosis, and non-Hispanic Black women had an aOR of 0.54 (95% CI 0.35-0.84). We also observed a difference in diagnosis by health insurance: compared to those with private insurance or Medi-Gap coverage, those with Medicare or military insurance had an aOR for endometriosis diagnosis of 2.49 (95% CI 1.36-4.55). Finally, compared to those with less than a high school education, those who had completed high school or greater had an aOR for endometriosis diagnosis of 2.84 (95% CI 1.15-6.99). CONCLUSION: These disparities in endometriosis diagnosis suggest that intersecting barriers may preclude certain groups from accessing timely endometriosis diagnosis and management. Further studies are warranted to explore these hypothesis-generating data and to identify and address specific barriers to equitable endometriosis diagnosis and management.


Asunto(s)
Endometriosis , Humanos , Endometriosis/diagnóstico , Endometriosis/epidemiología , Femenino , Estados Unidos/epidemiología , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven
14.
J Am Soc Nephrol ; 34(10): 1647-1671, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37725437

RESUMEN

SIGNIFICANCE STATEMENT: Hypoxia drives kidney damage and progression of CKD. Although erythrocytes respond rapidly to hypoxia, their role and the specific molecules sensing and responding to hypoxia in CKD remain unclear. In this study, we demonstrated in a mouse model that erythrocyte ENT1-AMPD3 is a master energy regulator of the intracellular purinergic hypoxic compensatory response that promotes rapid energy supply from extracellular adenosine, eAMPK-dependent metabolic reprogramming, and O 2 delivery, which combat renal hypoxia and progression of CKD. ENT1-AMPD3-AMPK-BPGM comprise a group of circulating erythroid-specific biomarkers, providing early diagnostic and novel therapeutic targets for CKD. BACKGROUND: Hypoxia drives kidney damage and progression of CKD. Although erythrocytes respond rapidly to hypoxia, their role and the specific molecules sensing and responding to hypoxia in CKD remain unclear. METHODS: Mice with an erythrocyte-specific deficiency in equilibrative nucleoside transporter 1 ( eEnt1-/- ) and a global deficiency in AMP deaminase 3 ( Ampd3-/- ) were generated to define their function in two independent CKD models, including angiotensin II (Ang II) infusion and unilateral ureteral obstruction (UUO). Unbiased metabolomics, isotopic adenosine flux, and various biochemical and cell culture analyses coupled with genetic studies were performed. Translational studies in patients with CKD and cultured human erythrocytes examined the role of ENT1 and AMPD3 in erythrocyte function and metabolism. RESULTS: eEnt1-/- mice display severe renal hypoxia, kidney damage, and fibrosis in both CKD models. The loss of eENT1-mediated adenosine uptake reduces intracellular AMP and thus abolishes the activation of AMPK α and bisphosphoglycerate mutase (BPGM). This results in reduced 2,3-bisphosphoglycerate and glutathione, leading to overwhelming oxidative stress in eEnt1-/- mice. Excess reactive oxygen species (ROS) activates AMPD3, resulting in metabolic reprogramming and reduced O 2 delivery, leading to severe renal hypoxia in eEnt1-/- mice. By contrast, genetic ablation of AMPD3 preserves the erythrocyte adenine nucleotide pool, inducing AMPK-BPGM activation, O 2 delivery, and antioxidative stress capacity, which protect against Ang II-induced renal hypoxia, damage, and CKD progression. Translational studies recapitulated the findings in mice. CONCLUSION: eENT1-AMPD3, two highly enriched erythrocyte purinergic components that sense hypoxia, promote eAMPK-BPGM-dependent metabolic reprogramming, O 2 delivery, energy supply, and antioxidative stress capacity, which mitigates renal hypoxia and CKD progression.


Asunto(s)
AMP Desaminasa , Insuficiencia Renal Crónica , Humanos , Ratones , Animales , Proteínas Quinasas Activadas por AMP/metabolismo , Hipoxia/metabolismo , Adenosina/metabolismo , Eritrocitos/metabolismo , Insuficiencia Renal Crónica/metabolismo , AMP Desaminasa/genética , AMP Desaminasa/metabolismo
15.
BMC Med Educ ; 24(1): 136, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38347486

RESUMEN

BACKGROUND: The management of low back pain (LBP) is highly variable and patients often receive management that is not recommended and/or miss out on recommended care. Clinician knowledge and behaviours are strongly influenced by entry-level clinical training and are commonly cited as barriers to implementing evidence-based management. Currently there are no internationally recognised curriculum standards for the teaching of LBP content to ensure graduating clinicians have the appropriate knowledge and competencies to assess and manage LBP. We formed an international interdisciplinary working group to develop curriculum content standards for the teaching of LBP in entry-level clinical training programs. METHODS: The working group included representatives from 11 countries: 18 academics and clinicians from healthcare professions who deal with the management of LBP (medicine, physiotherapy, chiropractic, osteopathy, pharmacology, and psychology), seven professional organisation representatives (medicine, physiotherapy, chiropractic, spine societies), and one healthcare consumer. A literature review was performed, including database and hand searches of guidelines and accreditation, curricula, and other policy documents, to identify gaps in current LBP teaching and recommended entry-level knowledge and competencies. The steering group (authors) drafted the initial LBP Curriculum Content Standards (LBP-CCS), which were discussed and modified through two review rounds with the working group. RESULTS: Sixty-two documents informed the draft standards. The final LBP-CCS consisted of four broad topics covering the epidemiology, biopsychosocial contributors, assessment, and management of LBP. For each topic, key knowledge and competencies to be achieved by the end of entry-level clinical training were described. CONCLUSION: We have developed the LBP-CCS in consultation with an interdisciplinary, international working group. These standards can be used to inform or benchmark the content of curricula related to LBP in new or existing entry-level clinical training programs.


Asunto(s)
Dolor de la Región Lumbar , Humanos , Dolor de la Región Lumbar/terapia , Curriculum , Atención a la Salud , Personal de Salud
16.
J Obstet Gynaecol ; 44(1): 2393359, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39176454

RESUMEN

BACKGROUND: To assess if implementation of the 2010 Patient Protection and Affordable Care Act (ACA) was associated with changes in the prevalence of women having ever received a pap smear. METHODS: This study utilised the publicly available Centre for Disease Control National Survey of Family Growth (NSFG) data set. This was a serial cross-sectional study. The comparison groups were defined as women who received cancer screening and prevention interventions prior to full implementation of the ACA (2011-2013) and post full implementation (2017-2019). The primary outcome was self-reporting receipt of a Papanicolaou (Pap) smear. Secondary outcomes included HPV vaccination and mammogram rates. Anonymized patient information was collected from the nationally representative dataset, and analyses were performed utilising STATA 18. RESULTS: The two study cohorts obtained from the NSFG included women who responded in 2011-2013 (n = 5601), deemed to be 'Pre-ACA implementation' (Pre ACA), and those who responded in 2017-2019 (n = 6141) 'Post-ACA implementation' (Post ACA). The proportion of women who were 21 years and older and ever had a Pap smear in the Pre ACA group (96.0%) was higher than that of the Post ACA group (94.1%) (OR 0.66 (0.49-0.91)). In contrast, HPV vaccination rates rose, and mammogram rates remained stable in the Post ACA period. CONCLUSION: A decrease in proportion of women ever having had a Pap smear despite implementation of health policies to increase access to preventive measures suggests further interventions to improve access to cervical cancer screening are warranted.


The Patient Protection and Affordable Care Act, which was implemented in 2014, aimed to reform health care access. This serial cross-sectional study demonstrated that the number of women age 21 or older who had ever received a pap smear fell after the implementation of the Patient Protection and Affordable Care Act.


Asunto(s)
Detección Precoz del Cáncer , Prueba de Papanicolaou , Patient Protection and Affordable Care Act , Neoplasias del Cuello Uterino , Humanos , Femenino , Prueba de Papanicolaou/estadística & datos numéricos , Patient Protection and Affordable Care Act/estadística & datos numéricos , Adulto , Estudios Transversales , Adulto Joven , Detección Precoz del Cáncer/estadística & datos numéricos , Estados Unidos , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/diagnóstico , Prevalencia , Persona de Mediana Edad , Frotis Vaginal/estadística & datos numéricos , Vacunas contra Papillomavirus/administración & dosificación , Mamografía/estadística & datos numéricos
17.
J Community Psychol ; 52(6): 720-738, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38843405

RESUMEN

Research has linked broad societal changes related to the COVID-19 pandemic and poorer mental health in young people. There remains a pressing need for studies examining the factors that are associated with better mental health and well-being. The current study addresses this gap using a community-based survey called the Waterloo Region Youth Impact Survey. It was designed in partnership with local youth and the Canadian Index of Well-Being in accordance with United Nations International Children's Emergency Fund guidelines. Using a convenience sampling methodology, this survey was developed to explore the domains, rates, and correlates of well-being and mental health among youth during the pandemic (N = 297). Confirmatory factor analysis was used to identify dimensions related to children's social environment (friends, school, family), sense of belonging, mental health, and well-being. Subsequently, a mediation model was tested. The relationship between children's environments and mental health and well-being operated via perceived sense of belonging. Findings shed light on patterns of youth mental health and well-being during the pandemic, illustrating the role of belonging as a promotive factor with public health relevance.


Asunto(s)
COVID-19 , Salud Mental , Humanos , COVID-19/psicología , COVID-19/epidemiología , Femenino , Masculino , Adolescente , Canadá/epidemiología , Niño , Encuestas y Cuestionarios , SARS-CoV-2 , Medio Social , Adulto Joven
18.
Phys Rev Lett ; 131(12): 120603, 2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37802959

RESUMEN

We propose a measurement-based model for fault-tolerant quantum computation that can be realized with one-dimensional cluster states and fusion measurements only; basic resources that are readily available with scalable photonic hardware. Our simulations demonstrate high thresholds compared with other measurement-based models realized with basic entangled resources and 2-qubit fusion measurements. Its high tolerance to noise indicates that our practical construction offers a promising route to scalable quantum computing with quantum emitters and linear-optical elements.

19.
Sex Transm Dis ; 50(11): 726-730, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-36943788

RESUMEN

BACKGROUND: Preexposure prophylaxis (PrEP) for HIV is disproportionately underprescribed to women. Centers for Disease Control and Prevention guidelines identify a group of women at risk of HIV acquisition who should be offered PrEP, but opportunities remain to improve patient awareness of and provider counseling about PrEP and to expand service delivery of PrEP. METHODS: Using nationally representative data from the 2017-2019 National Survey of Family Growth, we compared women with (n = 689) and without (n = 5,452) Centers for Disease Control and Prevention indications for PrEP on measures of PrEP awareness, counseling by a provider, and interaction with the health care system. RESULTS: Women with PrEP indications were no more likely to report awareness of PrEP (odds ratio [OR], 1.03; 95% confidence interval [CI], 0.82-1.29) or PrEP counseling by a provider (OR, 1.32; 95% CI, 0.77-2.27), compared with those without PrEP indications. However, women with PrEP indications were more likely than those without to report a birth control visit (OR, 1.82; 95% CI, 1.39-2.38) or an abortion within the last 12 months (OR, 5.93; 95% CI, 1.48-23.73), and to currently use prescription contraception (OR, 1.45; 95% CI, 1.19-1.78). A majority of both groups reported accessing prenatal care within the last 12 months. CONCLUSIONS: There remains a gap in PrEP awareness and counseling among women at highest risk for HIV acquisition. Sexual and reproductive health visits represent a logical and feasible venue for PrEP provision. Obstetrician-gynecologists and other family planning providers may be able to aid in service delivery innovations by providing PrEP alongside other sexual and reproductive health care.

20.
Epidemiol Infect ; 151: e171, 2023 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-37750016

RESUMEN

In this short report, we describe an outbreak of COVID-19 caused by Omicron subvariant BA.5.2.1 in highly vaccinated patients in a respiratory ward in a large acute general hospital in North West London, United Kingdom. The attack rate was high (14/33 (42%)) but the clinical impact was relatively non-severe including in patients who were at high risk of severe COVID-19. Twelve of fourteen patients had COVID-19 vaccinations. There was only one death due to COVID-19 pneumonitis. The findings of this outbreak investigation suggest that while the transmissibility of Omicron BA.5.2.1 subvariant is high, infections caused by this strain are non-severe in vaccinated patients, even if they are at high risk of severe COVID-19 infection.


Asunto(s)
COVID-19 , Infección Hospitalaria , Humanos , SARS-CoV-2 , Infección Hospitalaria/epidemiología , COVID-19/epidemiología , Hospitales Generales , Brotes de Enfermedades
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