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1.
Surg Endosc ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693306

RESUMO

BACKGROUND: There is no consensus on whether laparoscopic experience should be a prerequisite for robotic training. Further, there is limited information on skill transference between laparoscopic and robotic techniques. This study focused on the general surgery residents' learning curve and skill transference within the two minimally invasive platforms. METHODS: General surgery residents were observed during the performance of laparoscopic and robotic inguinal hernia repairs. The recorded data included objective measures (operative time, resident participation indicated by percent active time on console or laparoscopy relative to total case time, number of handoffs between the resident and attending), and subjective evaluations (preceptor and trainee assessments of operative performance) while controlling for case complexity, patient comorbidities, and residents' prior operative experience. Wilcoxon two-sample tests and Pearson Correlation coefficients were used for analysis. RESULTS: Twenty laparoscopic and forty-four robotic cases were observed. Mean operative times were 90 min for robotic and 95 min for laparoscopic cases (P = 0.4590). Residents' active participation time was 66% on the robotic platform and 37% for laparoscopic (P = < 0.0001). On average, hand-offs occurred 9.7 times during robotic cases and 6.3 times during laparoscopic cases (P = 0.0131). The mean number of cases per resident was 5.86 robotic and 1.67 laparoscopic (P = 0.0312). For robotic cases, there was a strong correlation between percent active resident participation and their prior robotic experience (r = 0.78) while there was a weaker correlation with prior laparoscopic experience (r = 0.47). On the other hand, prior robotic experience had minimal correlation with the percent active resident participation in laparoscopic cases (r = 0.12) and a weak correlation with prior laparoscopic experience (r = 0.37). CONCLUSION: The robotic platform may be a more effective teaching tool with a higher degree of entrustability indicated by the higher mean resident participation. We observed a greater degree of skill transference from laparoscopy to the robot, indicated by a higher degree of correlation between the resident's prior laparoscopic experience and the percent console time in robotic cases. There was minimal correlation between residents' prior robotic experience and their participation in laparoscopic cases. Our findings suggest that the learning curve for the robot may be shorter as prior robotic experience had a much stronger association with future robotic performance compared to the association observed in laparoscopy.

2.
Psychiatr Serv ; : appips20230489, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38693833

RESUMO

OBJECTIVE: The authors evaluated associations between employment at discharge from Veterans Health Administration Vocational Rehabilitation Service (VR) programs and suicide and other causes of death. METHODS: For veterans receiving VR between October 1, 2005, and September 30, 2014 (N=78,293), proportional hazards analyses were used to test associations of employment with suicide, drug overdose, and external and natural cause mortality rates over 1 and 5 years postdischarge and through December 31, 2019. The analyses were adjusted for clinical and sociodemographic characteristics and propensity for employment. RESULTS: Of the veterans, 94.1% had a psychiatric diagnosis, and 35.5% were employed at VR discharge. In proportional hazards analyses, employment was associated with lower mortality rates through 1 year (suicide, hazard ratio [HR]=0.54; overdose, HR=0.70; external causes, HR=0.62; and natural causes, HR=0.51) and 5 years postdischarge (overdose, HR=0.72; external causes, HR=0.81; and natural causes, HR=0.72). Through December 31, 2019, employment was associated with lower risks for overdose (HR=0.80) and death by external (HR=0.81) and natural (HR=0.80) causes. CONCLUSIONS: Employment at VR discharge was associated with lower mortality risk among veterans with psychiatric diagnoses.

3.
Am J Trop Med Hyg ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714193

RESUMO

The South Asia International Center of Excellence for Malaria Research, an NIH-funded collaborative program, investigated the epidemiology of malaria in the Indian state of Goa through health facility-based data collected from the Goa Medical College and Hospital (GMC), the state's largest tertiary healthcare facility, between 2012 and 2021. Our study investigated region-specific spatial and temporal patterns of malaria transmission in Goa and the factors driving such patterns. Over the past decade, the number of malaria cases, inpatients, and deaths at the GMC decreased significantly after a peak in 2014-2015. However, the proportion of severe malaria cases increased over the study period. Also, a trend of decreasing average parasitemia and increasing average gametocyte density suggests a shift toward submicroscopic infections and an increase in transmission commitment characteristic of low-transmission regions. Although transmission occurred throughout the year, 75% of the cases occurred between June and December, overlapping with the monsoon (June-October), which featured rainfall above yearly average, minimal diurnal temperature variation, and high relative humidity. Sociodemographic factors also had a significant association with malaria cases, with cases being more frequent in the 15-50-year-old age group, men, construction workers, and people living in urban areas within the GMC catchment region. Our environmental model of malaria transmission projects almost negligible transmission at the beginning of 2025 (annual parasitic index: 0.0095, 95% CI: 0.0075-0.0114) if the current control measures continue undisrupted.

4.
Prev Med ; : 107987, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38714274

RESUMO

OBJECTIVE: The present study examined reports of changing eating to manage weight/shape over one year among adolescents. It also tested how changing eating for weight/shape was associated with physical activity (resistance training, moderate-to-vigorous physical activity) and mental health (depressive symptoms, flourishing), and whether weight perceptions moderated these associations. METHODS: Participants were Canadian adolescents (N = 20,614, Mage ±â€¯SD = 14.4 ±â€¯1.3, 52.9% girls) who completed self-report surveys in the 2020-2021 and 2021-2022 waves of the COMPASS study. Separate multilevel models were tested for each outcome. RESULTS: Approximately 30% of adolescents reported changing their eating to manage weight/shape at least once a week. More days of changing eating were associated with significantly higher depressive symptoms and lower flourishing cross-sectionally (b = 0.51, b = -0.27) and over time (b = 0.35, -0.20); the flourishing association over time was weaker for adolescents who perceived themselves as overweight relative to about right. More days of changing eating were also associated with more MVPA and resistance training cross-sectionally (b = 2.81, b = 0.19) and over time (b = 1.28, b = 10). The relationship between changing eating and MVPA over time was stronger for adolescents who perceived themselves as overweight relative to about right; whereas the cross-sectional relationship between changing eating and resistance training was weaker. CONCLUSIONS: Reports of changing eating to manage weight/shape were associated with divergent health outcomes; research into how and to what extreme adolescents are changing eating to manage weight/shape, and identity factors that may contribute to these differences, is warranted.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38712546

RESUMO

We report on the latest advancements in Microcrystal Electron Diffraction (3D ED/MicroED), as discussed during a symposium at the National Center for CryoEM Access and Training housed at the New York Structural Biology Center. This snapshot describes cutting-edge developments in various facets of the field and identifies potential avenues for continued progress. Key sections discuss instrumentation access, research applications for small molecules and biomacromolecules, data collection hardware and software, data reduction software, and finally reporting and validation. 3D ED/MicroED is still early in its wide adoption by the structural science community with ample opportunities for expansion, growth, and innovation.

7.
Ann Plast Surg ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38717157

RESUMO

BACKGROUND: Despite growing demand for gender-affirming surgery (GAS), there are few formal GAS fellowships in the United States. Paucity of online information about GAS fellowships may discourage potential applicants and decrease the visibility of the field. Thus, it is important to analyze the existing online information about GAS fellowships to improve fellow recruitment and patient outcomes. OBJECTIVE: To identify the number of GAS fellowship websites (GASFWs) and evaluate their robustness. Second, to report the social media presence of GAS fellowships. METHODS: To identify GASFWs, existing databases sponsored by plastic surgery associations and Google query were used between April and May 2023. Thirty-five independent variables based on previously published data were evaluated for presence in a bivariate fashion on GASFWs. Accounts on popular social media websites were also identified by Google query. Website and social media analysis were also done for GAS fellowships that were offered by departments/specialties other than plastic surgery. RESULTS: In total, only 6 GASFWs associated with plastic surgery departments were identified and analyzed. Eight nonplastic surgery GASFWs were included for analysis. Overall, both categories of GASFWs were not robust; key information such as previous fellow listing and selection criteria was often missing. Furthermore, important topics specifically related to GAS such as community engagement and programmatic building are often not found on GASFWs either. In addition, none of the fellowships had any independent Facebook, Instagram, or Twitter. CONCLUSIONS: To ensure patient safety and quality outcomes, it is important to promote GAS by recruiting more applicants for specialized training beyond residency. With increased Internet use, improving GASFWs and social media presence as well as considering the use of a centralized database or match system can foster the growth of the field.

8.
ISME Commun ; 4(1): ycae051, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38699060

RESUMO

Soil carbon loss is likely to increase due to climate warming, but microbiomes and microenvironments may dampen this effect. In a 30-year warming experiment, physical protection within soil aggregates affected the thermal responses of soil microbiomes and carbon dynamics. In this study, we combined metagenomic analysis with physical characterization of soil aggregates to explore mechanisms by which microbial communities respond to climate warming across different soil microenvironments. Long-term warming decreased the relative abundances of genes involved in degrading labile compounds (e.g. cellulose), but increased those genes involved in degrading recalcitrant compounds (e.g. lignin) across aggregate sizes. These changes were observed in most phyla of bacteria, especially for Acidobacteria, Actinobacteria, Bacteroidetes, Chloroflexi, and Planctomycetes. Microbial community composition was considerably altered by warming, leading to declined diversity for bacteria and fungi but not for archaea. Microbial functional genes, diversity, and community composition differed between macroaggregates and microaggregates, indicating the essential role of physical protection in controlling microbial community dynamics. Our findings suggest that microbes have the capacity to employ various strategies to acclimate or adapt to climate change (e.g. warming, heat stress) by shifting functional gene abundances and community structures in varying microenvironments, as regulated by soil physical protection.

9.
eNeuro ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38719452

RESUMO

The corpus callosum is composed of several subregions, distinct in cellular and functional organization. This organization scheme may render these subregions differentially vulnerable to the aging process. Callosal integrity may be further compromised by cardiovascular risk factors, which negatively influence white matter health. Here, we test for heterochronicity of aging, hypothesizing an anterior-to-posterior gradient of vulnerability to aging that may be altered by effects of cardiovascular health. In 174 healthy adults across the adult lifespan (mean age=53.56 ± 18.90, range=20-94 years old, 58.62% women), pulse pressure (calculated as participant's systolic minus diastolic blood pressure) was assessed to determine cardiovascular risk. A deterministic tractography approach via diffusion weighted imaging was utilized to extract fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) from each of five callosal subregions, serving as estimates of microstructural health. General linear models tested effects of age, hypertension, and pulse pressure on these cross-sectional metrics. We observed no significant effect of hypertensive diagnosis on callosal microstructure. We found a significant main effect of age and an age x pulse pressure interaction whereby older age and elevated pulse pressure were associated with poorer FA, AD, and RD. Age effects revealed non-linear components and occurred along an anterior-posterior gradient of severity in the callosum. This gradient disappeared when pulse pressure was considered. These results indicate that age-related deterioration across the callosum is regionally variable, and that pulse pressure, a proxy of arterial stiffness, exacerbates this aging pattern in a large lifespan cohort.Significance Statement Aging is associated with microstructural changes in the corpus callosum, the largest white matter tract in the brain. Additionally, cardiovascular factors, such as hypertension and pulse pressure, affect corpus callosum microstructure. However, it is unclear whether these factors uniformly impact the corpus callosum throughout aging. The current study aimed to characterize patterns of corpus callosum aging and assess the influence of hypertension and pulse pressure across subregions of callosal white matter. We found an age-related gradient on corpus callosum microstructure, with the most pronounced impact on anterior regions. However, this gradient was absent when pulse pressure was considered. These findings suggest that callosal subregions are differentially sensitive to age-related decline, and pulse pressure modifies and exacerbates these declines.

10.
Occup Environ Med ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724253

RESUMO

We examined the association between mean birth weight (BW) differences and perfluorohexane sulfonate (PFHxS) exposure biomarkers.We fit a random effects model to estimate the overall pooled effect and for different strata based on biomarker sample timing and overall study confidence. We also conducted an analysis to examine the impact of a continuous measure of gestational age sample timing on the overall pooled effect.We detected a -7.9 g (95% CI -15.0 to -0.7; pQ=0.85; I2=0%) BW decrease per ln ng/mL PFHxS increase based on 27 studies. The 11 medium confidence studies (ß=-10.0 g; 95% CI -21.1 to 1.1) showed larger deficits than 12 high (ß=-6.8 g; 95% CI -16.3 to 2.8) and 4 low confidence studies (ß=-1.5 g; 95% CI -51.6 to 48.7). 10 studies with mid-pregnancy to late-pregnancy sampling periods showed smaller deficits (ß=-3.9 g; 95% CI -17.7 to 9.9) than 5 post-partum studies (ß=-28.3 g; 95% CI -69.3 to 12.7) and 12 early sampling studies (ß=-7.6 g; 95% CI -16.2 to 1.1). 6 of 12 studies with the earliest sampling timing showed results closer to the null.Overall, we detected a small but statistically significant BW deficit across 27 studies. We saw comparable BW deficit magnitudes in both the medium and high confidence studies as well as the early pregnancy group. Despite no definitive pattern by sample timing, larger deficits were seen in postpartum studies. We also saw results closer to the null for a subset of studies restricted to the earliest biomarker collection times. Serial pregnancy sampling, improved precision in gestational age estimates and more standardised reporting of sample variation and exposure units in future epidemiologic research may offer a greater understanding of the relationship between PFHxS on BW and any potential impact of pregnancy haemodynamics.

11.
Pediatr Dev Pathol ; : 10935266231223278, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38576417

RESUMO

Coronary artery anomalies and their potential sequelae are not well studied in association with stillbirth. Herein, we report the autopsy findings in two term stillborn fetuses with coronary artery anomalies. Both fetuses showed identical findings consisting of an abnormal origin of the left coronary artery from the right sinus of Valsalva and an interarterial course of the left coronary artery. Histologic vascular and myocardial changes were also present. These coronary artery findings are associated with sudden death in adults and neonates, and therefore, their potential to be a cause and/or contributor to fetal death is suspected.

12.
Infect Control Hosp Epidemiol ; : 1-3, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38561199

RESUMO

A clinical decision support system, EvalMpox, was developed to apply person under investigation (PUI) criteria for patients presenting with rash and to recommend testing for PUIs. Of 668 patients evaluated, an EvalMpox recommendation for testing had a positive predictive value of 35% and a negative predictive value of 99% for a positive mpox test.

13.
Int J Mol Sci ; 25(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38612581

RESUMO

Chronic primary systemic vasculitis (PSV) comprises a group of heterogeneous diseases that are broadly classified by affected blood vessel size, clinical traits and the presence (or absence) of anti-neutrophil cytoplasmic antibodies (ANCA) against proteinase 3 (PR3) and myeloperoxidase (MPO). In small vessel vasculitis (SVV), ANCA are not present in all patients, and they are rarely detected in patients with vasculitis involving medium (MVV) and large (LVV) blood vessels. Some studies have demonstrated that lysosome-associated membrane protein-2 (LAMP-2/CD107b) is a target of ANCA in SVV, but its presence and prognostic value in childhood MVV and LVV is not known. This study utilized retrospective sera and clinical data obtained from 90 children and adolescents with chronic PSV affecting small (SVV, n = 53), medium (MVV, n = 16), and large (LVV, n = 21) blood vessels. LAMP-2-ANCA were measured in time-of-diagnosis sera using a custom electrochemiluminescence assay. The threshold for seropositivity was established in a comparator cohort of patients with systemic autoinflammatory disease. The proportion of LAMP-2-ANCA-seropositive individuals and sera concentrations of LAMP-2-ANCA were assessed for associations with overall and organ-specific disease activity at diagnosis and one-year follow up. This study demonstrated a greater time-of-diagnosis prevalence and sera concentration of LAMP-2-ANCA in MVV (52.9% seropositive) and LVV (76.2%) compared to SVV (45.3%). Further, LAMP-2-ANCA-seropositive individuals had significantly lower overall, but not organ-specific, disease activity at diagnosis. This did not, however, result in a greater reduction in disease activity or the likelihood of achieving inactive disease one-year after diagnosis. The results of this study demonstrate particularly high prevalence and concentration of LAMP-2-ANCA in chronic PSV that affects large blood vessels and is seronegative for traditional ANCA. Our findings invite reconsideration of roles for autoantigens other than MPO and PR3 in pediatric vasculitis, particularly in medium- and large-sized blood vessels.


Assuntos
Vasculite Sistêmica , Vasculite , Adolescente , Humanos , Criança , Anticorpos Anticitoplasma de Neutrófilos , Estudos Retrospectivos , Autoantígenos , Mieloblastina
14.
Sex Transm Dis ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38647252

RESUMO

BACKGROUND: Productivity costs of STIs reflect the value of lost time due to STI morbidity and mortality, including time spent travelling to, waiting for, and receiving STI treatment. The purpose of this study was to provide updated estimates of the average lifetime productivity cost for chlamydia, gonorrhea, and syphilis, per incident infection. METHODS: We adapted published decision tree models from recent studies of the lifetime medical costs of chlamydia, gonorrhea, and syphilis in the United States. For each possible outcome of infection, we applied productivity costs that we obtained based on published health economic studies. Productivity costs included the value of patient time spent to receive treatment for STIs and for related sequelae such as pelvic inflammatory disease in women. We used a human capital approach and included losses in market (paid) and non-market (unpaid) productivity. We conducted one-way sensitivity analyses and probabilistic sensitivity analyses. RESULTS: The average lifetime productivity cost per infection was $28 for chlamydia in men, $205 for chlamydia in women, $37 for gonorrhea in men, $212 for gonorrhea in women, and $411 for syphilis regardless of sex, in 2023 US dollars. The estimated lifetime productivity costs of these STIs acquired in the United States in 2018 was $795 million. CONCLUSIONS: These estimates of the lifetime productivity costs can help in quantifying the overall economic burden of STIs in the United States beyond just the medical cost burden and can inform cost-effectiveness analyses of STI prevention activities.

15.
Pediatr Obes ; : e13118, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38676448

RESUMO

BACKGROUND: Internalized weight bias (IWB) has been identified as a correlate of higher depressive and anxiety symptoms in adolescents with higher weights. However, there has been limited investigation into how IWB relates to positive mental health and whether these associations differ across genders. OBJECTIVES: To examine the associations between IWB and mental health (depression, anxiety, flourishing) in adolescents with higher weights, and to test the potential moderating role of gender. METHODS: Canadian adolescents with higher weights (N = 7538, 60% boys, 36% girls, 4% gender diverse, ages 12-19) from the COMPASS study completed a survey during the 2021-2022 school year. Data were analysed using generalized linear models. RESULTS: Highest IWB and poorest mental health were noted within gender diverse adolescents, followed by girls then boys. Gender moderated the relationship between higher IWB and higher depression, higher anxiety and lower flourishing, with the strongest relationships noted among girls. CONCLUSION: IWB interventions should be tailored to gender subgroups that may be particularly vulnerable to maladaptive mental health outcomes associated with IWB. System-level changes that mitigate perpetuation of weight bias and discrimination which lead to IWB are also essential, particularly for girls.

17.
J Infect Dis ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640957

RESUMO

Chlamydia trachomatis (CT) is a sexually transmitted infection that can lead to adverse reproductive health outcomes. CT prevalence estimates are primarily derived from screening using nucleic acid amplification tests (NAATs). However, screening guidelines in the United States only include particular subpopulations, and NAATs only detect current infections. In contrast, seroassays identify past CT infections which are important for understanding the public health impacts of CT, including pelvic inflammatory disease and tubal factor infertility. Older seroassays have been plagued by low sensitivity and specificity and have not been validated using a consistent reference measure, making it challenging to compare studies, define the epidemiology of CT and determine the effectiveness of control programs. Newer seroassays have better performance characteristics. This narrative review summarizes the "state of the science" for CT seroassays that have been applied in epidemiologic studies and provides practical considerations for interpreting the literature and employing seroassays in future research.

18.
PLoS One ; 19(4): e0293680, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38652715

RESUMO

Universal and early recognition of pathogens occurs through recognition of evolutionarily conserved pathogen associated molecular patterns (PAMPs) by innate immune receptors and the consequent secretion of cytokines and chemokines. The intrinsic complexity of innate immune signaling and associated signal transduction challenges our ability to obtain physiologically relevant, reproducible and accurate data from experimental systems. One of the reasons for the discrepancy in observed data is the choice of measurement strategy. Immune signaling is regulated by the interplay between pathogen-derived molecules with host cells resulting in cellular expression changes. However, these cellular processes are often studied by the independent assessment of either the transcriptome or the proteome. Correlation between transcription and protein analysis is lacking in a variety of studies. In order to methodically evaluate the correlation between transcription and protein expression profiles associated with innate immune signaling, we measured cytokine and chemokine levels following exposure of human cells to the PAMP lipopolysaccharide (LPS) from the Gram-negative pathogen Pseudomonas aeruginosa. Expression of 84 messenger RNA (mRNA) transcripts and 69 proteins, including 35 overlapping targets, were measured in human lung epithelial cells. We evaluated 50 biological replicates to determine reproducibility of outcomes. Following pairwise normalization, 16 mRNA transcripts and 6 proteins were significantly upregulated following LPS exposure, while only five (CCL2, CSF3, CXCL5, CXCL8/IL8, and IL6) were upregulated in both transcriptomic and proteomic analysis. This lack of correlation between transcription and protein expression data may contribute to the discrepancy in the immune profiles reported in various studies. The use of multiomic assessments to achieve a systems-level understanding of immune signaling processes can result in the identification of host biomarker profiles for a variety of infectious diseases and facilitate countermeasure design and development.


Assuntos
Biomarcadores , Células Epiteliais , Lipopolissacarídeos , Pseudomonas aeruginosa , Humanos , Lipopolissacarídeos/farmacologia , Células Epiteliais/metabolismo , Células Epiteliais/imunologia , Pseudomonas aeruginosa/imunologia , Biomarcadores/metabolismo , Pulmão/metabolismo , Pulmão/imunologia , Transcriptoma , Citocinas/metabolismo , Perfilação da Expressão Gênica , Imunidade Inata , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcrição Gênica/efeitos dos fármacos , Quimiocinas/metabolismo , Quimiocinas/genética
19.
Neural Comput ; 36(5): 781-802, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38658027

RESUMO

Variation in the strength of synapses can be quantified by measuring the anatomical properties of synapses. Quantifying precision of synaptic plasticity is fundamental to understanding information storage and retrieval in neural circuits. Synapses from the same axon onto the same dendrite have a common history of coactivation, making them ideal candidates for determining the precision of synaptic plasticity based on the similarity of their physical dimensions. Here, the precision and amount of information stored in synapse dimensions were quantified with Shannon information theory, expanding prior analysis that used signal detection theory (Bartol et al., 2015). The two methods were compared using dendritic spine head volumes in the middle of the stratum radiatum of hippocampal area CA1 as well-defined measures of synaptic strength. Information theory delineated the number of distinguishable synaptic strengths based on nonoverlapping bins of dendritic spine head volumes. Shannon entropy was applied to measure synaptic information storage capacity (SISC) and resulted in a lower bound of 4.1 bits and upper bound of 4.59 bits of information based on 24 distinguishable sizes. We further compared the distribution of distinguishable sizes and a uniform distribution using Kullback-Leibler divergence and discovered that there was a nearly uniform distribution of spine head volumes across the sizes, suggesting optimal use of the distinguishable values. Thus, SISC provides a new analytical measure that can be generalized to probe synaptic strengths and capacity for plasticity in different brain regions of different species and among animals raised in different conditions or during learning. How brain diseases and disorders affect the precision of synaptic plasticity can also be probed.


Assuntos
Teoria da Informação , Plasticidade Neuronal , Sinapses , Animais , Sinapses/fisiologia , Plasticidade Neuronal/fisiologia , Espinhas Dendríticas/fisiologia , Região CA1 Hipocampal/fisiologia , Modelos Neurológicos , Armazenamento e Recuperação da Informação , Masculino , Hipocampo/fisiologia , Ratos
20.
Sci Adv ; 10(14): eadj9305, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38569042

RESUMO

The power and scope of disease modeling can be markedly enhanced through the incorporation of broad genetic diversity. The introduction of pathogenic mutations into a single inbred mouse strain sometimes fails to mimic human disease. We describe a cross-species precision disease modeling platform that exploits mouse genetic diversity to bridge cell-based modeling with whole organism analysis. We developed a universal protocol that permitted robust and reproducible neural differentiation of genetically diverse human and mouse pluripotent stem cell lines and then carried out a proof-of-concept study of the neurodevelopmental gene DYRK1A. Results in vitro reliably predicted the effects of genetic background on Dyrk1a loss-of-function phenotypes in vivo. Transcriptomic comparison of responsive and unresponsive strains identified molecular pathways conferring sensitivity or resilience to Dyrk1a1A loss and highlighted differential messenger RNA isoform usage as an important determinant of response. This cross-species strategy provides a powerful tool in the functional analysis of candidate disease variants identified through human genetic studies.


Assuntos
Células-Tronco Pluripotentes , Animais , Camundongos , Humanos , Fenótipo
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