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1.
Mol Ecol ; 33(11): e17363, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38682794

RESUMO

Hybridisation can be an important driver of evolutionary change, but hybridisation with invasive species can have adverse effects on native biodiversity. While hybridisation has been documented across taxa, there is limited understanding of ecological factors promoting patterns of hybridisation and the spatial distribution of hybrid individuals. We combined the results of ecological niche modelling (ENM) and restriction site-associated DNA sequencing to test theories of niche conservatism and biotic resistance on the success of invasion, admixture, and extent of introgression between native and non-native fishes. We related Maxent predictions of habitat suitability based on the native ranges of invasive Eastern Banded Killifish (Fundulus diaphanus diaphanus Lesueur 1817) and native Western Banded Killifish (Fundulus diaphanus menona Jordan and Copeland 1877) to admixture indices of individual Banded Killifish. We found that Eastern Banded Killifish predominated at sites predicted as suitable from their ENM, consistent with niche conservatism. Admixed individuals were more common as Eastern Banded Killifish habitat suitability declined. We also found that Eastern Banded Killifish were most common at sites closest to the presumed source of this invasion, whereas the proportion of admixed individuals increased with distance from the source of invasion. Lastly, we found little evidence that habitat suitability for Western Banded Killifish provides biotic resistance from either displacement by, or admixture with, invasive Eastern Banded Killifish. Our study demonstrates that ENMs can inform conservation-relevant outcomes between native and invasive taxa while emphasising the importance of protecting isolated Western Banded Killifish populations from invasive conspecifics.


Assuntos
Ecossistema , Fundulidae , Espécies Introduzidas , Animais , Fundulidae/genética , Hibridização Genética , Genética Populacional , Introgressão Genética , Análise de Sequência de DNA , Biodiversidade
2.
Curr Biol ; 34(8): 1731-1738.e3, 2024 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-38593800

RESUMO

In face-to-face interactions with infants, human adults exhibit a species-specific communicative signal. Adults present a distinctive "social ensemble": they use infant-directed speech (parentese), respond contingently to infants' actions and vocalizations, and react positively through mutual eye-gaze and smiling. Studies suggest that this social ensemble is essential for initial language learning. Our hypothesis is that the social ensemble attracts attentional systems to speech and that sensorimotor systems prepare infants to respond vocally, both of which advance language learning. Using infant magnetoencephalography (MEG), we measure 5-month-old infants' neural responses during live verbal face-to-face (F2F) interaction with an adult (social condition) and during a control (nonsocial condition) in which the adult turns away from the infant to speak to another person. Using a longitudinal design, we tested whether infants' brain responses to these conditions at 5 months of age predicted their language growth at five future time points. Brain areas involved in attention (right hemisphere inferior frontal, right hemisphere superior temporal, and right hemisphere inferior parietal) show significantly higher theta activity in the social versus nonsocial condition. Critical to theory, we found that infants' neural activity in response to F2F interaction in attentional and sensorimotor regions significantly predicted future language development into the third year of life, more than 2 years after the initial measurements. We develop a view of early language acquisition that underscores the centrality of the social ensemble, and we offer new insight into the neurobiological components that link infants' language learning to their early brain functioning during social interaction.


Assuntos
Encéfalo , Desenvolvimento da Linguagem , Magnetoencefalografia , Interação Social , Humanos , Lactente , Masculino , Feminino , Encéfalo/fisiologia , Atenção/fisiologia , Fala/fisiologia
3.
bioRxiv ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38617350

RESUMO

Signaling through the platelet-derived growth factor receptor alpha (PDGFRa) plays a critical role in craniofacial development, as mutations in PDGFRA are associated with cleft lip/palate in humans and Pdgfra mutant mouse models display varying degrees of facial clefting. Phosphatidylinositol 3-kinase (PI3K)/Akt is the primary effector of PDGFRα signaling during skeletal development in the mouse. We previously demonstrated that Akt phosphorylates the RNA-binding protein serine/arginine-rich splicing factor 3 (Srsf3) downstream of PI3K-mediated PDGFRa signaling in mouse embryonic palatal mesenchyme (MEPM) cells, leading to its nuclear translocation. We further showed that ablation of Srsf3 in the murine neural crest lineage results in severe midline facial clefting, due to defects in proliferation and survival of cranial neural crest cells, and widespread alternative RNA splicing (AS) changes. Here, we sought to determine the molecular mechanisms by which Srsf3 activity is regulated downstream of PDGFRa signaling to control AS of transcripts necessary for craniofacial development. We demonstrated via enhanced UV-crosslinking and immunoprecipitation (eCLIP) of MEPM cells that PDGF-AA stimulation leads to preferential binding of Srsf3 to exons and loss of binding to canonical Srsf3 CA-rich motifs. Through the analysis of complementary RNA-seq data, we showed that Srsf3 activity results in the preferential inclusion of exons with increased GC content and lower intron to exon length ratio. Moreover, we found that the subset of transcripts that are bound by Srsf3 and undergo AS upon PDGFRα signaling commonly encode regulators of PI3K signaling and early endosomal trafficking. Functional validation studies further confirmed that Srsf3 activity downstream of PDGFRα signaling leads to retention of the receptor in early endosomes and increases in downstream PI3K-mediated Akt signaling. Taken together, our findings reveal that growth factor-mediated phosphorylation of an RNA-binding protein underlies gene expression regulation necessary for mammalian craniofacial development.

4.
Brain Res Bull ; 212: 110958, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38677559

RESUMO

Education sculpts specialized neural circuits for skills like reading that are critical to success in modern society but were not anticipated by the selective pressures of evolution. Does the emergence of brain regions that selectively process novel visual stimuli like words occur at the expense of cortical representations of other stimuli like faces and objects? "Neuronal Recycling" predicts that learning to read should enhance the response to words in ventral occipitotemporal cortex (VOTC) and decrease the response to other visual categories such as faces and objects. To test this hypothesis, and more broadly to understand the changes that are induced by the early stages of literacy instruction, we conducted a randomized controlled trial with pre-school children (five years of age). Children were randomly assigned to intervention programs focused on either reading skills or oral language skills and magnetoencephalography (MEG) data collected before and after the intervention was used to measure visual responses to images of text, faces, and objects. We found that being taught reading versus oral language skills induced different patterns of change in category-selective regions of visual cortex, but that there was not a clear tradeoff between the response to words versus other categories. Within a predefined region of VOTC corresponding to the visual word form area (VWFA) we found that the relative amplitude of responses to text, faces, and objects changed, but increases in the response to words were not linked to decreases in the response to faces or objects. How these changes play out over a longer timescale is still unknown but, based on these data, we can surmise that high-level visual cortex undergoes rapid changes as children enter school and begin establishing new skills like literacy.

5.
Am J Drug Alcohol Abuse ; : 1-11, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563523

RESUMO

Background: Cannabis use is associated with altered processing of external (exteroceptive) and internal (interoceptive) sensory stimuli. However, little research exists on whether subjective experiences of these processes are altered in people who frequently use cannabis. Altered exteroception may influence externally oriented attention, whereas interoceptive differences have implications for intoxication, craving, and withdrawal states.Objectives: The goal of the current study was to investigate subjective experiences of exteroceptive sensory gating and interoception in people frequently using cannabis. We hypothesized subjective impairments in sensory gating and elevations in affect-related interoceptive awareness; furthermore, such deviations would relate to cannabis use patterns.Methods: This cross-sectional study of community adults 18-40 years old included 72 individuals (50% female) who used cannabis at least twice a week (not intoxicated during study) and 78 individuals who did not use cannabis (60% female). Participants completed the Sensory Gating Inventory and the Multidimensional Assessment of Interoceptive Awareness-2 surveys. People using cannabis completed surveys on cannabis use patterns. Analyses tested group differences and associations with cannabis use.Results: People using cannabis reported impaired sensory gating (d = 0.37-0.44; all p values < 0.05) and elevations of interoceptive awareness related to detection and affect (d = 0.21-0.61; all p values < 0.05). Problematic cannabis use was associated with increased sensory gating impairments (r = 0.37, p < .05). Interoceptive awareness was unrelated to cannabis use variables.Conclusion: These findings extend literature on subjective experiences of sensory processing in people using cannabis. Findings may inform inclusion of external attentional tendencies and internal bodily awareness in assessments of risk and novel treatment approaches.

6.
J Wrist Surg ; 13(2): 171-175, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38505207

RESUMO

Background Perilunate dislocations are devastating injuries that occur relatively rarely, accounting for only 7% of injuries to the carpus. Unfortunately, approximately 25% of these injuries are missed on initial evaluation. Acutely diagnosed perilunate dislocations may be successfully treated with ligament and osseous repair, depending on the injury pattern. Chronic dislocations, however, are primarily treated with salvage procedures. This case series was performed to investigate the outcomes of patients who sustained a perilunate dislocation that was diagnosed in a delayed fashion and look for any treatment patterns that could be more widely applied to future patients. Methods Patients presenting to a single institution between 2016 and 2018 with a perilunate injury that either presented in a delayed fashion or was missed on initial assessment were identified and their characteristics were evaluated. The surgical management of these patients was assessed as was their postoperative course at their 2-week, 6-week, 3-month, and 6-month clinic follow-up visits. Results Eight patients were identified with perilunate dislocations that were diagnosed in a delayed fashion. On average, these dislocations were diagnosed 133 days following the date of injury. All patients were males and 7/8 of them were between 17 and 20 years of age at the time of their injury (mean age: 25.5). They were treated with either primary repair, wrist fusion, proximal row carpectomy, or scaphoid excision and four-corner fusion (SEFCF). Both pain and range of motion improved following surgical management of these injuries. Conclusion Perilunate dislocations are rare injuries that are notorious for being diagnosed late, at which point primary repair is oftentimes no longer feasible. Salvage procedures are able to improve the range of motion and pain of patients who are found to have chronic dislocations. Our case series highlights the importance of treating each missed perilunate injury individually and avoiding a "one-size-fits-all" approach.

7.
Int Psychogeriatr ; : 1-6, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38462965

RESUMO

Prolonged grief disorder (PGD) is associated with impairments in cognitive functioning, but the neuropsychological correlates of early grief in older adults are poorly understood. This preliminary study cross-sectionally examined neuropsychological functioning in bereaved adults with high and low grief symptoms and a non-bereaved comparison sample and further explored the relationship between multidomain cognitive measures and grief severity. A total of ninety-three nondemented older adults (high grief: n = 44; low grief: n = 49) within 12 months post-bereavement and non-bereaved comparison participants (n = 43) completed neuropsychological battery including global and multiple domain-specific cognitive functioning. Linear regression models were used to analyze differences in multidomain cognitive measures between the groups and specifically examine the associations between cognitive performance and grief severity in the bereaved, after covariate adjustment, including depressive symptoms. Bereaved older adults with higher grief symptoms performed worse than those with lower symptoms and non-bereaved participants on executive functioning and attention and processing speed measures. In the bereaved, poorer executive functioning, attention and processing speed correlated with higher grief severity. Attention/processing speed-grief severity correlation was seen in those with time since loss ≤ 6 months, but not > 6 months. Intense early grief is characterised by poorer executive functioning, attention, and processing speed, resembling findings in PGD. The putative role of poorer cognitive functioning during early grief on the transition to integrated grief or the development of PGD remains to be elucidated.

8.
Br J Radiol ; 97(1155): 614-621, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38303547

RESUMO

OBJECTIVES: To compare brain MRI measures between Adult Changes in Thought (ACT) participants who underwent research, clinical, or both MRI scans, and clinical health measures across the groups and non-MRI subjects. METHODS: Retrospective cohort study leveraging MRI, clinical, demographic, and medication data from ACT. Three neuroradiologists reviewed MRI scans using NIH Neuroimaging Common Data Elements (CDEs). Total brain and white matter hyperintensity (WMH) volumes, clinical characteristics, and outcome measures of brain and overall health were compared between groups. 1166 MRIs were included (77 research, 1043 clinical, and 46 both) and an additional 3146 participants with no MRI were compared. RESULTS: Compared to the group with research MRI only, the clinical MRI group had higher prevalence of the following: acute infarcts, chronic haematoma, subarachnoid haemorrhage, subdural haemorrhage, haemorrhagic transformation, and hydrocephalus (each P < .001). Quantitative WMH burden was significantly lower (P < .001) and total brain volume significantly higher (P < .001) in research MRI participants compared to other MRI groups. Prevalence of hypertension, self-reported cerebrovascular disease, congestive heart failure, dementia, and recent hospitalization (all P < .001) and diabetes (P = .002) differed significantly across groups, with smaller proportions in the research MRI group. CONCLUSION: In ageing populations, significant differences were observed in MRI metrics between research MRI and clinical MRI groups, and clinical health metric differences between research MRI, clinical MRI, and no-MRI groups. ADVANCES IN KNOWLEDGE: This questions whether research cohorts can adequately represent the greater ageing population undergoing imaging. These findings may also be useful to radiologists when interpreting neuroimaging of ageing.


Assuntos
Encéfalo , Transtornos Cerebrovasculares , Adulto , Humanos , Estudos Retrospectivos , Encéfalo/diagnóstico por imagem , Envelhecimento , Neuroimagem , Imageamento por Ressonância Magnética/métodos
9.
Environ Int ; 183: 108418, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38185046

RESUMO

BACKGROUND: While epidemiologic evidence links higher levels of exposure to fine particulate matter (PM2.5) to decreased cognitive function, fewer studies have investigated links with traffic-related air pollution (TRAP), and none have examined ultrafine particles (UFP, ≤100 nm) and late-life dementia incidence. OBJECTIVE: To evaluate associations between TRAP exposures (UFP, black carbon [BC], and nitrogen dioxide [NO2]) and late-life dementia incidence. METHODS: We ascertained dementia incidence in the Seattle-based Adult Changes in Thought (ACT) prospective cohort study (beginning in 1994) and assessed ten-year average TRAP exposures for each participant based on prediction models derived from an extensive mobile monitoring campaign. We applied Cox proportional hazards models to investigate TRAP exposure and dementia incidence using age as the time axis and further adjusting for sex, self-reported race, calendar year, education, socioeconomic status, PM2.5, and APOE genotype. We ran sensitivity analyses where we did not adjust for PM2.5 and other sensitivity and secondary analyses where we adjusted for multiple pollutants, applied alternative exposure models (including total and size-specific UFP), modified the adjustment covariates, used calendar year as the time axis, assessed different exposure periods, dementia subtypes, and others. RESULTS: We identified 1,041 incident all-cause dementia cases in 4,283 participants over 37,102 person-years of follow-up. We did not find evidence of a greater hazard of late-life dementia incidence with elevated levels of long-term TRAP exposures. The estimated hazard ratio of all-cause dementia was 0.98 (95 % CI: 0.92-1.05) for every 2000 pt/cm3 increment in UFP, 0.95 (0.89-1.01) for every 100 ng/m3 increment in BC, and 0.96 (0.91-1.02) for every 2 ppb increment in NO2. These findings were consistent across sensitivity and secondary analyses. DISCUSSION: We did not find evidence of a greater hazard of late-life dementia risk with elevated long-term TRAP exposures in this population-based prospective cohort study.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Demência , Adulto , Humanos , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Exposição Ambiental/análise , Estudos Prospectivos , Dióxido de Nitrogênio/análise , Incidência , Material Particulado/análise , Demência/epidemiologia
10.
Neurology ; 102(3): e208060, 2024 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-38175995

RESUMO

BACKGROUND AND OBJECTIVES: The aim of this study was to compare 2 large clinicopathologic cohorts of participants aged 90+ and to determine whether the association between neuropathologic burden and dementia in these older groups differs substantially from those seen in younger-old adults. METHODS: Autopsied participants from The 90+ Study and Adult Changes in Thought (ACT) Study community-based cohort studies were evaluated for dementia-associated neuropathologic changes. Associations between neuropathologic variables and dementia were assessed using logistic or linear regression, and the weighted population attributable fraction (PAF) per type of neuropathologic change was estimated. RESULTS: The 90+ Study participants (n = 414) were older (mean age at death = 97.7 years) and had higher amyloid/tau burden than ACT <90 (n = 418) (mean age at death = 83.5 years) and ACT 90+ (n = 401) (mean age at death = 94.2 years) participants. The ACT 90+ cohort had significantly higher rates of limbic-predominant age-related TDP-43 encephalopathy (LATE-NC), microvascular brain injury (µVBI), and total neuropathologic burden. Independent associations between individual neuropathologic lesions and odds of dementia were similar between all 3 groups, with the exception of µVBI, which was associated with increased dementia risk in the ACT <90 group only (odds ratio 1.5, 95% CI 1.2-1.8, p < 0.001). Weighted PAF scores indicated that eliminating µVBI, although more prevalent in ACT 90+ participants, would have little effect on dementia. Conversely, eliminating µVBI in ACT <90 could theoretically reduce dementia at a similar rate to that of AD neuropathologic change (weighted PAF = 6.1%, 95% CI 3.8-8.4, p = 0.001). Furthermore, reducing LATE-NC in The 90+ Study could potentially reduce dementia to a greater degree (weighted PAF = 5.1%, 95% CI 3.0-7.3, p = 0.001) than either ACT cohort (weighted PAFs = 1.69, 95% CI 0.4-2.7). DISCUSSION: Our results suggest that specific neuropathologic features may differ in their effect on dementia among nonagenarians and centenarians from cohorts with different selection criteria and study design. Furthermore, microvascular lesions seem to have a more significant effect on dementia in younger compared with older participants. The results from this study demonstrate that different populations may require distinct dementia interventions, underscoring the need for disease-specific biomarkers.


Assuntos
Doença de Alzheimer , Demência , Doenças do Sistema Nervoso , Idoso de 80 Anos ou mais , Humanos , Doença de Alzheimer/patologia , Encéfalo/patologia , Centenários , Nonagenários , Demência/epidemiologia , Demência/patologia , Doenças do Sistema Nervoso/patologia
11.
JAMA Intern Med ; 184(1): 54-62, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38010725

RESUMO

Importance: Modifiable risk factors are hypothesized to account for 30% to 40% of dementia; yet, few trials have demonstrated that risk-reduction interventions, especially multidomain, are efficacious. Objective: To determine if a personalized, multidomain risk reduction intervention improves cognition and dementia risk profile among older adults. Design, Setting, and Participants: The Systematic Multi-Domain Alzheimer Risk Reduction Trial was a randomized clinical trial with a 2-year personalized, risk-reduction intervention. A total of 172 adults at elevated risk for dementia (age 70-89 years and with ≥2 of 8 targeted risk factors) were recruited from primary care clinics associated with Kaiser Permanente Washington. Data were collected from August 2018 to August 2022 and analyzed from October 2022 to September 2023. Intervention: Participants were randomly assigned to the intervention (personalized risk-reduction goals with health coaching and nurse visits) or to a health education control. Main Outcomes and Measures: The primary outcome was change in a composite modified Neuropsychological Test Battery; preplanned secondary outcomes were change in risk factors and quality of life (QOL). Outcomes were assessed at baseline and 6, 12, 18, and 24 months. Linear mixed models were used to compare, by intention to treat, average treatment effects (ATEs) from baseline over follow-up. The intervention and outcomes were initially in person but then, due to onset of the COVID-19 pandemic, were remote. Results: The 172 total participants had a mean (SD) age of 75.7 (4.8) years, and 108 (62.8%) were women. After 2 years, compared with the 90 participants in the control group, the 82 participants assigned to intervention demonstrated larger improvements in the composite cognitive score (ATE of SD, 0.14; 95% CI, 0.03-0.25; P = .02; a 74% improvement compared with the change in the control group), better composite risk factor score (ATE of SD, 0.11; 95% CI, 0.01-0.20; P = .03), and improved QOL (ATE, 0.81 points; 95% CI, -0.21 to 1.84; P = .12). There were no between-group differences in serious adverse events (24 in the intervention group and 23 in the control group; P = .59), but the intervention group had greater treatment-related adverse events such as musculoskeletal pain (14 in the intervention group vs 0 in the control group; P < .001). Conclusions and Relevance: In this randomized clinical trial, a 2-year, personalized, multidomain intervention led to modest improvements in cognition, dementia risk factors, and QOL. Modifiable risk-reduction strategies should be considered for older adults at risk for dementia. Trial Registration: ClinicalTrials.gov Identifier: NCT03683394.


Assuntos
Demência , Qualidade de Vida , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Pandemias , Cognição , Comportamento de Redução do Risco , Demência/prevenção & controle , Demência/epidemiologia
12.
JAMA Netw Open ; 6(10): e2340249, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37902753

RESUMO

Importance: High visit-to-visit blood pressure variability (BPV) in late life may reflect increased dementia risk better than mean systolic blood pressure (SBP). Evidence from midlife to late life could be crucial to understanding this association. Objective: To determine whether visit-to-visit BPV at different ages was differentially associated with lifetime incident dementia risk in community-dwelling individuals. Design, Setting, and Participants: This cohort study analyzed data from the Adult Changes in Thought (ACT) study, an ongoing population-based prospective cohort study in the US. Participants were 65 years or older at enrollment, community-dwelling, and without dementia. The study focused on a subset of deceased participants with brain autopsy data and whose midlife to late-life blood pressure data were obtained from Kaiser Permanente Washington medical archives and collected as part of the postmortem brain donation program. In the ACT study, participants underwent biennial medical assessments, including cognitive screening. Data were collected from 1994 (ACT study enrollment) through November 2019 (data set freeze). Data analysis was performed between March 2020 and September 2023. Exposures: Visit-by-visit BPV at ages 60, 70, 80, and 90 years, calculated using the coefficient of variation of year-by-year SBP measurements over the preceding 10 years. Main Outcomes and Measures: All-cause dementia, which was adjudicated by a multidisciplinary outcome adjudication committee. Results: A total of 820 participants (mean [SD] age at enrollment, 77.0 [6.7] years) were analyzed and included 476 females (58.0%). A mean (SD) of 28.4 (8.4) yearly SBP measurements were available over 31.5 (9.0) years. The mean (SD) follow-up time was 32.2 (9.1) years in 27 885 person-years from midlife to death. Of the participants, 372 (45.4%) developed dementia. The number of participants who were alive without dementia and had available data for analysis ranged from 280 of those aged 90 years to 702 of those aged 70 years. Higher BPV was not associated with higher lifetime dementia risk at age 60, 70, or 80 years. At age 90 years, BPV was associated with 35% higher dementia risk (hazard ratio [HR], 1.35; 95% CI, 1.02-1.79). Meta-regression of HRs calculated separately for each age (60-90 years) indicated that associations of high BPV with higher dementia risk were present only at older ages, whereas the association of SBP with dementia gradually shifted direction linearly from being incrementally to inversely associated with older ages. Conclusions and Relevance: In this cohort study, high BPV indicated increased lifetime dementia risk in late life but not in midlife. This result suggests that high BPV may indicate increased dementia risk in older age but might be less viable as a midlife dementia prevention target.


Assuntos
Demência , Hipertensão , Adulto , Feminino , Humanos , Idoso de 80 Anos ou mais , Pressão Sanguínea , Estudos de Coortes , Estudos Prospectivos , Hipertensão/epidemiologia , Demência/epidemiologia
13.
Neurosci Insights ; 18: 26331055231201600, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37810186

RESUMO

Studying proteomics data of the human brain could offer numerous insights into unraveling the signature of resilience to Alzheimer's disease. In our previous study with rigorous cohort selection criteria that excluded 4 common comorbidities, we harnessed multiple brain regions from 43 research participants with 12 of them displaying cognitive resilience to Alzheimer's disease. Based on the previous findings, this work focuses on 6 proteins out of the 33 differentially expressed proteins associated with resilience to Alzheimer's disease. These proteins are used to construct a decision tree classifier, enabling the differentiation of 3 groups: (i) healthy control, (ii) resilience to Alzheimer's disease, and (iii) Alzheimer's disease with dementia. Our analysis unveiled 2 important regional proteomic markers: Aß peptides in the hippocampus and PA1B3 in the inferior parietal lobule. These findings underscore the potential of using distinct regional proteomic markers as signatures in characterizing the resilience to Alzheimer's disease.

14.
JBJS Case Connect ; 13(3)2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37590436

RESUMO

CASE: Olecranon fractures treated with proximal ulna plate fixation and repairing the triceps with suture augmentation to the plate decrease the risk of "olecranon escape," but may lead to failure through triceps rupture. In this case report, a rare complication of triceps rupture occurred, and the patient underwent triceps repair. CONCLUSION: When fixing olecranon fractures, surgeons should minimize triceps dissection for hardware placement. If subjected to significant force, a surgical insult to the tendon footprint for a better plate contact on the bone and the presence of suture augmentation may change the construct failure mechanism and result in triceps rupture as opposed to fracture redisplacement.


Assuntos
Olécrano , Fraturas da Ulna , Humanos , Olécrano/cirurgia , Procedimentos Neurocirúrgicos , Epífises , Tendões , Fraturas da Ulna/cirurgia , Suturas
15.
Environ Sci Technol ; 57(41): 15336-15347, 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37647613

RESUMO

The Inflation Reduction Act (IRA) in the United States provides unprecedented incentives for deploying low-carbon hydrogen and liquid fuels, among other low-greenhouse gas (GHG) emissions technologies. To better understand the prospective competitiveness of low-carbon or negative-carbon hydrogen and liquid fuels under the IRA in the early 2030s, we examined the impacts of the IRA provisions on the costs of producing hydrogen and synthetic liquid fuel made from natural gas, electricity, short-cycle biomass (agricultural residues), and corn-derived ethanol. We determined that, with IRA credits (45V or 45Q) but excluding the incentives provided by other national or state policies, hydrogen produced by electrolysis using carbon-free electricity (green H2) and by natural gas reforming with carbon capture and storage (CCS) (blue H2) is cost-competitive with the carbon-intensive benchmark gray H2, which is produced by steam methane reforming. Biomass-derived H2 with or without CCS is not cost-competitive under the current IRA provisions. However, if the IRA allowed biomass gasification with CCS to claim a 45V credit for carbon-neutral H2 and a 45Q credit for negative biogenic CO2 emissions, this pathway would be less costly than gray H2. The IRA credit for clean fuels (45Z), currently stipulated to end in 2027, would need to be extended or similar policy support would need to be provided by other national or state policies in order for clean synthetic liquid fuel to be cost-competitive with petroleum-derived liquid fuels. The levelized IRA subsidies per unit of CO2 mitigated for all of the hydrogen and synthetic liquid fuel production pathways, except for electricity-derived synthetic liquid fuel, range from $65-$384/t of CO2. These values are within or below the range of the U.S. federal government's estimates of the social cost of carbon (SCC) in the 2030-2040 time frame.

17.
Brain Topogr ; 36(5): 686-697, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37393418

RESUMO

BACKGROUND: Functional near-infrared spectroscopy (fNIRS) is a viable non-invasive technique for functional neuroimaging in the cochlear implant (CI) population; however, the effects of acoustic stimulus features on the fNIRS signal have not been thoroughly examined. This study examined the effect of stimulus level on fNIRS responses in adults with normal hearing or bilateral CIs. We hypothesized that fNIRS responses would correlate with both stimulus level and subjective loudness ratings, but that the correlation would be weaker with CIs due to the compression of acoustic input to electric output. METHODS: Thirteen adults with bilateral CIs and 16 with normal hearing (NH) completed the study. Signal-correlated noise, a speech-shaped noise modulated by the temporal envelope of speech stimuli, was used to determine the effect of stimulus level in an unintelligible speech-like stimulus between the range of soft to loud speech. Cortical activity in the left hemisphere was recorded. RESULTS: Results indicated a positive correlation of cortical activation in the left superior temporal gyrus with stimulus level in both NH and CI listeners with an additional correlation between cortical activity and perceived loudness for the CI group. The results are consistent with the literature and our hypothesis. CONCLUSIONS: These results support the potential of fNIRS to examine auditory stimulus level effects at a group level and the importance of controlling for stimulus level and loudness in speech recognition studies. Further research is needed to better understand cortical activation patterns for speech recognition as a function of both stimulus presentation level and perceived loudness.


Assuntos
Córtex Auditivo , Implantes Cocleares , Percepção da Fala , Adulto , Humanos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Córtex Auditivo/diagnóstico por imagem , Córtex Auditivo/fisiologia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiologia , Estimulação Acústica
18.
J Physician Assist Educ ; 34(3): 178-187, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37467205

RESUMO

PURPOSE: The purpose of this study was to describe practices and experiences of rurally oriented physician assistant (PA) training programs in providing rural clinical training to PA students. METHODS: A survey of PA program directors (PDs) included questions about program characteristics, student and clinical preceptor (CP) recruitment in rural areas, and barriers to, and facilitators of, rural clinical training. Programs that considered rural training "very important" to their goals were identified. We interviewed PDs from rurally oriented programs about their rural clinical training and rural CPs about their experiences training PA students for rural practice. We identified key themes through content analysis. RESULTS: Of 178 programs surveyed, 113 (63.5%) responded, 61 (54.0%) of which were rurally oriented and more likely than other programs to recruit rural students or those with rural practice interests and to address rural issues in didactic curriculum. The 13 PDs interviewed linked successful rural training to finding and supporting rural preceptors who enjoy teaching and helping students understand rural communities. The 13 rural CPs identified enthusiastic and rurally interested students as key elements to successful rural training. Interviewees identified systemic barriers to rural training, including student housing, decreased productivity, competition for training slots, and administrative burden. CONCLUSIONS: Physician assistant students can be coached to capitalize on their rural clinical experiences. Knowing how to "jump in" to rotations and having genuine interest in the community are particularly important. Student housing, competition for training slots, and lack of financial incentives are major system-level challenges for sustaining and increasing the availability of PA rural clinical training.


Assuntos
Assistentes Médicos , População Rural , Humanos , Assistentes Médicos/educação , Estudantes , Currículo , Inquéritos e Questionários
19.
Psychol Serv ; 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37261763

RESUMO

Although psychologists are trained to conduct research as well as clinical work, it can be challenging for psychologists outside of traditional academia to find the time or capacity to engage in research. Providing opportunities for practicing psychologists to conduct research may enhance the generalizability of psychological research, as well as provide benefits to psychologists in terms of collaboration, promotion, and engagement. Yet, several barriers exist, including competing demands on time, lack of institutional support, and limited research confidence. This article describes "Paper in a Day" (PiaD), a novel approach to research engagement that is well-suited for busy practitioners. PiaD considers many of the aforementioned factors and provides a method to navigate the often-daunting prospect of research involvement for the practicing clinician. Through PiaD, two Department of Veterans Affairs (VA) Medical Centers engaged clinicians and trainees in collaborating in a time-limited way to write and publish peer-reviewed articles. The current article outlines the process by which clinicians at these two sites structured research engagement utilizing PiaD, and it was also written utilizing the PiaD model. The authors have now led or participated in the PiaD process five times, with 13 teams of clinicians producing nine peer-reviewed articles and five conference presentations. A brief survey indicated that participants felt engaged in the process and would participate again if given the opportunity. This article outlines barriers and facilitators of the PiaD process, with the hope of encouraging other settings to consider using such a method to enhance research productivity and engagement for psychologists. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

20.
Nat Med ; 29(7): 1662-1670, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37322115

RESUMO

Clonal hematopoiesis of indeterminate potential (CHIP) is a premalignant expansion of mutated hematopoietic stem cells. As CHIP-associated mutations are known to alter the development and function of myeloid cells, we hypothesized that CHIP may also be associated with the risk of Alzheimer's disease (AD), a disease in which brain-resident myeloid cells are thought to have a major role. To perform association tests between CHIP and AD dementia, we analyzed blood DNA sequencing data from 1,362 individuals with AD and 4,368 individuals without AD. Individuals with CHIP had a lower risk of AD dementia (meta-analysis odds ratio (OR) = 0.64, P = 3.8 × 10-5), and Mendelian randomization analyses supported a potential causal association. We observed that the same mutations found in blood were also detected in microglia-enriched fraction of the brain in seven of eight CHIP carriers. Single-nucleus chromatin accessibility profiling of brain-derived nuclei in six CHIP carriers revealed that the mutated cells comprised a large proportion of the microglial pool in the samples examined. While additional studies are required to validate the mechanistic findings, these results suggest that CHIP may have a role in attenuating the risk of AD.


Assuntos
Doença de Alzheimer , Lesões Pré-Cancerosas , Humanos , Hematopoiese Clonal , Doença de Alzheimer/genética , Hematopoese/genética , Células-Tronco Hematopoéticas , Mutação/genética
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