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1.
Sci Adv ; 10(14): eadl0389, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38569044

RESUMEN

The dynamin-related guanosine triphosphatase, Drp1 (encoded by Dnm1l), plays a central role in mitochondrial fission and is requisite for numerous cellular processes; however, its role in muscle metabolism remains unclear. Here, we show that, among human tissues, the highest number of gene correlations with DNM1L is in skeletal muscle. Knockdown of Drp1 (Drp1-KD) promoted mitochondrial hyperfusion in the muscle of male mice. Reduced fatty acid oxidation and impaired insulin action along with increased muscle succinate was observed in Drp1-KD muscle. Muscle Drp1-KD reduced complex II assembly and activity as a consequence of diminished mitochondrial translocation of succinate dehydrogenase assembly factor 2 (Sdhaf2). Restoration of Sdhaf2 normalized complex II activity, lipid oxidation, and insulin action in Drp1-KD myocytes. Drp1 is critical in maintaining mitochondrial complex II assembly, lipid oxidation, and insulin sensitivity, suggesting a mechanistic link between mitochondrial morphology and skeletal muscle metabolism, which is clinically relevant in combatting metabolic-related diseases.


Asunto(s)
Insulinas , Succinato Deshidrogenasa , Animales , Humanos , Masculino , Ratones , Insulinas/metabolismo , Lípidos , Mitocondrias/genética , Mitocondrias/metabolismo , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Músculo Esquelético/metabolismo , Succinato Deshidrogenasa/metabolismo
2.
JAMA Neurol ; 81(5): 534-548, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38466294

RESUMEN

Importance: Multiple continuous intravenous anesthetic drugs (CIVADs) are available for the treatment of refractory status epilepticus (RSE). There is a paucity of data comparing the different types of CIVADs used for RSE. Objective: To systematically review and compare outcome measures associated with the initial CIVAD choice in RSE in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Evidence Review: Data sources included English and non-English articles using Embase, MEDLINE, PubMed, and Web of Science (January 1994-June 2023) as well as manual search. Study selection included peer-reviewed studies of 5 or more patients and at least 1 patient older than 12 years with status epilepticus refractory to a benzodiazepine and at least 1 standard antiseizure medication, treated with continuously infused midazolam, ketamine, propofol, pentobarbital, or thiopental. Independent extraction of articles was performed using prespecified data items. The association between outcome variables and CIVAD was examined with an analysis of variance or χ2 test where appropriate. Binary logistic regressions were used to examine the association between outcome variables and CIVAD with etiology, change in mortality over time, electroencephalography (EEG) monitoring (continuous vs intermittent), and treatment goal (seizure vs burst suppression) included as covariates. Risk of bias was addressed by listing the population and type of each study. Findings: A total of 66 studies with 1637 patients were included. Significant differences among CIVAD groups in short-term failure, hypotension, and CIVAD substitution during treatment were observed. Non-epilepsy-related RSE (vs epilepsy-related RSE) was associated with a higher rate of CIVAD substitution (60 of 120 [50.0%] vs 11 of 43 [25.6%]; odds ratio [OR], 3.11; 95% CI, 1.44-7.11; P = .006) and mortality (98 of 227 [43.2%] vs 7 of 63 [11.1%]; OR, 17.0; 95% CI, 4.71-109.35; P < .001). Seizure suppression was associated with mortality (OR, 7.72; 95% CI, 1.77-39.23; P = .005), but only a small subgroup was available for analysis (seizure suppression: 17 of 22 [77.3%] from 3 publications vs burst suppression: 25 of 98 [25.5%] from 12 publications). CIVAD choice and EEG type were not predictors of mortality. Earlier publication year was associated with mortality, although the observation was no longer statistically significant after adjusting SEs for clustering. Conclusions and Relevance: Epilepsy-related RSE was associated with lower mortality compared with other RSE etiologies. A trend of decreasing mortality over time was observed, which may suggest an effect of advances in neurocritical care. The overall data are heterogeneous, which limits definitive conclusions on the choice of optimal initial CIVAD in RSE treatment.


Asunto(s)
Anestésicos Intravenosos , Epilepsia Refractaria , Estado Epiléptico , Humanos , Estado Epiléptico/tratamiento farmacológico , Anestésicos Intravenosos/administración & dosificación , Anestésicos Intravenosos/uso terapéutico , Epilepsia Refractaria/tratamiento farmacológico , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/administración & dosificación
3.
Nicotine Tob Res ; 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38365185

RESUMEN

INTRODUCTION: Cigarette and little cigar/cigarillo (LCC) dual use is popular among young people and poses a substantial health risk. What remains unclear is the abuse liability of LCCs vs. cigarettes, LCCs' substitutability for cigarettes, and the influence of flavors on the abuse liability and substitutability of LCCs. METHODS: Sixty-five young adults (18-34 years) who dual use completed hypothetical purchase tasks to measure consumption of usual brand cigarettes and LCCs in 24h at increasing prices (demand), and LCC consumption at increasing cigarette prices (substitution). Three demand indices were calculated from raw data: breakpoint (price after which consumption reaches 0), Omax (maximum daily expenditure), and Pmax (price at maximum expenditure). Two indices were estimated using nonlinear mixed-effects modeling: intensity (consumption when free), and price-sensitivity (rate of decline in consumption as price increases). Substitution, and associations of flavored use with demand and substitution, were estimated using linear mixed models. RESULTS: Results indicated similar abuse liability for LCCs and cigarettes. Intensity was greater for cigarettes, but price-sensitivity was similar. Flavored LCC use was associated with lower price-sensitivity and greater intensity than unflavored. LCCs were significant substitutes for cigarettes, but the effect was small. Flavored use was not associated with substitution. CONCLUSIONS: Among young adults who dual use, LCCs and cigarettes had similar abuse liability, and those who used flavored had higher demand for their LCCs. A flavored cigar ban, as well as targeted prevention and cessation services for those who smoke flavored LCCs, may be important for reducing dual use in young adults. IMPLICATIONS: Cigarette and little cigar/cigarillo (LCC) dual use remains high among young adults. Using hypothetical purchase tasks with young adults who dual use, LCCs had abuse liability similar to cigarettes, but were only modest substitutes for cigarettes. Participants who used flavored LCCs reported greater abuse liability than those who used unflavored, but not greater substitution for cigarettes. Prevention and cessation services are needed to target LCCs in young people, particularly those smoking flavored products. A flavored cigar ban may help to reduce their demand.

4.
Int J Mol Sci ; 25(2)2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38255925

RESUMEN

As the kynurenine pathway's links to inflammation, the immune system, and neurological disorders became more apparent, it attracted more and more attention. It is the main pathway through which the liver breaks down Tryptophan and the initial step in the creation of nicotinamide adenine dinucleotide (NAD+) in mammals. Immune system activation and the buildup of potentially neurotoxic substances can result from the dysregulation or overactivation of this pathway. Therefore, it is not shocking that kynurenines have been linked to neurological conditions (Depression, Parkinson's, Alzheimer's, Huntington's Disease, Schizophrenia, and cognitive deficits) in relation to inflammation. Nevertheless, preclinical research has demonstrated that kynurenines are essential components of the behavioral analogs of depression and schizophrenia-like cognitive deficits in addition to mediators associated with neurological pathologies due to their neuromodulatory qualities. Neurodegenerative diseases have been extensively associated with neuroactive metabolites of the kynurenine pathway (KP) of tryptophan breakdown. In addition to being a necessary amino acid for protein synthesis, Tryptophan is also transformed into the important neurotransmitters tryptamine and serotonin in higher eukaryotes. In this article, a summary of the KP, its function in neurodegeneration, and the approaches being used currently to target the route therapeutically are discussed.


Asunto(s)
Trastornos del Conocimiento , Quinurenina , Animales , Triptófano , Aminoácidos , Inflamación , Mamíferos
5.
Behav Modif ; 48(2): 216-256, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38197303

RESUMEN

Self-injurious behavior (SIB) among children and youth with developmental disabilities has not diminished in prevalence despite the availability of effective interventions, and the impact on quality of life for people and their families is devastating. The current meta-analysis reviews SIB intervention research between 2011 and 2021 using single-case experimental designs with children and youth up to 21 years old and provides a quantitative synthesis of data from high-quality studies including moderator analyses to determine effects of participant and study characteristics on intervention outcomes. Encouraging findings include a high level of effectiveness across studies in the decrease of SIB (Tau-U = -0.90) and increase of positive behavior (Tau-U = 0.73), as well as an increase in studies (relative to prior reviews) reporting intervention fidelity, generalization, maintenance, and social validity. However, our findings shed limited light on potential moderating variables in the development of interventions for children and youth who exhibit SIB. Of the potential moderators of intervention effects, only implementer (researcher/therapist vs. parent/caregiver) and setting (clinic vs. home) were significantly associated with improved outcomes. We discuss the need for more robust involvement of natural communities of implementers in SIB intervention research to better equip them to effectively and sustainably meet the needs of people they care for. We also discuss the importance of creating systems enabling broad access for children with SIB to effective interventions in service of reducing burden for people, families, and society over time.


Asunto(s)
Discapacidades del Desarrollo , Conducta Autodestructiva , Niño , Humanos , Adolescente , Discapacidades del Desarrollo/complicaciones , Discapacidades del Desarrollo/terapia , Calidad de Vida , Padres , Conducta Autodestructiva/complicaciones , Conducta Autodestructiva/terapia
6.
Int J Paediatr Dent ; 34(2): 125-134, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37330621

RESUMEN

BACKGROUND: Panoramic radiographs (PRs) are used in the detection and diagnosis of developmental dental anomalies and pathologies (DDAPs) in children. AIM: The primary objective of this observational cohort study was to evaluate the age-based prevalence of DDAP on PRs, whereas the secondary objective was to determine a threshold age for the detection of DDAP to provide supportive evidence for the prescription of PR in paediatric dental practice. DESIGN: The study examined diagnostic PRs from 581 subjects aged 6 to 19 years. All PRs were reviewed by experienced, calibrated, masked examiners for the identification or presence of anomalies in size, shape, position, structure, and other developmental anomalies and pathologies (ODAP) of the face-neck region in a standardized condition. The data were statistically analyzed for interpretation. RESULTS: Overall, 74% (n = 411) of the cohort had at least one anomaly (shape anomaly: 12%, number anomaly: 17%, positional anomaly: 28%, structural anomaly: 0%, and ODAP: 63%). The optimal Youden index cutoff for any anomaly was 9 years. Twelve and 15 years also showed predictive ability. CONCLUSION: The results suggest that PRs should be prescribed at ages 9, 12, and 15 years for the diagnosis of DDAP.


Asunto(s)
Anomalías Dentarias , Diente Impactado , Humanos , Niño , Anomalías Dentarias/diagnóstico por imagen , Anomalías Dentarias/epidemiología , Radiografía Panorámica , Prevalencia , Prescripciones
7.
Am J Prev Med ; 66(1): 18-26, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37709155

RESUMEN

INTRODUCTION: The federal Child and Adult Care Food Program (CACFP) improves nutrition and reduces food insecurity among young children by helping cover the food costs for child care providers and families. This nationwide study evaluated the extent and predictors of the CACFP's utilization among licensed child care centers to identify opportunities for expanding CACFP nutrition support. METHODS: Administrative data from the CACFP and child care licensing agencies in 47 states and District of Columbia were compiled and geocoded for 93,227 licensed child care centers. CACFP participation was predicted using a multivariable Bayesian spatial logistic regression model in the sample of low-income areas to target CACFP eligible child care centers. Data were collected in 2020-2021 and analyzed in 2022. RESULTS: Of all licensed child care centers, 36.5% participated in the CACFP, ranging from 15.2% to 65.3% across states; when restricted to low-income areas, 57.5% participated (range, 15.7%-85.7%). Income differences did not explain the large variation in CACFP participation rates across states. Having at least three CACFP sponsoring agencies per state predicted a 38% higher probability of CACFP participation (OR=1.38; 95% Credible Interval=1.08-1.78). CONCLUSIONS: Currently CACFP participation rates among licensed child care centers point to program underutilization and unequal access, particularly in some states and regions. Work at the federal and state levels is warranted to expand participation in the program, above all in low-income areas, so that more young children could eat healthfully with the CACFP.


Asunto(s)
Asistencia Alimentaria , Estado Nutricional , Adulto , Niño , Humanos , Preescolar , Teorema de Bayes , Guarderías Infantiles , Cuidado del Niño , Alimentos , Política Nutricional
8.
Injury ; 54(12): 111129, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37880032

RESUMEN

INTRODUCTION: Recidivism is common following injury. Interventions to enhance patient engagement may reduce trauma recidivism. Education, counseling, peer mentorship, and other resources are known as Trauma Recovery Services (TRS). The authors hypothesized that TRS use would reduce trauma recidivism. METHODS: Over five years at a level 1 trauma center, 954 adults treated operatively for pelvic, spine, and femoral fractures were reviewed. Recidivism was defined as return to trauma center for new injury within 30-months. All patients were offered TRS. Multivariate logistic regression statistical analysis was used to identify predictors of recidivism. RESULTS: Three hundred and ninety-seven of all patients (42 %) utilized TRS, including educational materials (n = 293), peer visits (n = 360), coaching (n = 284), posttraumatic stress disorder (PTSD) screening (n = 74), and other services. Within the entire sample, 136 patients (14 %) returned to the emergency department for an unrelated trauma event after mean 21 months. 13 % of TRS users became recidivists. Overall, 49 % of recidivists had history of pre-existing mental illness. High rates of TRS engagement between recidivists and non-recidivists were seen (75 %); however, non-recidivists were more likely to use multiple types of recovery services (49 % vs 34 %, p = 0.002), and were more likely to engage with trauma peer mentors (former trauma survivors) more than once (91 % vs 81 %, p = 0.03). After multivariable analysis, patients using multiple different recovery services had a lower risk of recidivism (p = 0.04, OR 0.42, 95 % CI [0.19-0.96]). CONCLUSIONS: Multifaceted engagement with recovery programming is associated with less recidivism following trauma. Future study of resultant reductions in healthcare costs are warranted. LEVEL OF EVIDENCE: Level II; Prognostic.


Asunto(s)
Ortopedia , Adulto , Humanos , Predicción , Pronóstico , Modelos Logísticos , Centros Traumatológicos
9.
Soft Matter ; 19(36): 7011-7019, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37671647

RESUMEN

Entropy compartmentalization provides new self-assembly routes to colloidal host-guest (HG) structures. Leveraging host particle shape to drive the assembly of HG structures has only recently been proposed and demonstrated. However, the extent to which the guest particles can dictate the structure of the porous network of host particles has not been explored. In this work, by modifying only the guest shape, we show athermal, binary mixtures of star-shaped host particles and convex polygon-shaped guest particles assemble as many as five distinct crystal structures, including rotator and discrete rotator guest crystals, two homoporous host crystals, and one heteroporous host crystal. Edge-to-edge alignment of neighboring stars results in the formation of three distinct pore motifs, whose preferential formation is controlled by the size and shape of the guest particles. Finally, we confirm, via free volume calculations, that assembly is driven by entropy compartmentalization, where the hosts and guests contribute differently to the free energy of the system; free volume calculations also explain differences in assembly based on guest shape. These results provide guest design rules for assembling colloidal HG structures, especially on surfaces and interfaces.

10.
Acta Biochim Biophys Sin (Shanghai) ; 55(8): 1153-1167, 2023 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-37357527

RESUMEN

Severe acute respiratory syndrome (SARS)-CoV-2 virus causes novel coronavirus disease 2019 (COVID-19), and there is a possible role for oxidative stress in the pathophysiology of neurological diseases associated with COVID-19. Excessive oxidative stress could be responsible for the thrombosis and other neuronal dysfunctions observed in COVID-19. This review discusses the role of oxidative stress associated with SARS-CoV-2 and the mechanisms involved. Furthermore, the various therapeutics implicated in treating COVID-19 and the oxidative stress that contributes to the etiology and pathogenesis of COVID-19-induced neuronal dysfunction are discussed. Further mechanistic and clinical research to combat COVID-19 is warranted to understand the exact mechanisms, and its true clinical effects need to be investigated to minimize neurological complications from COVID-19.


Asunto(s)
COVID-19 , Enfermedades del Sistema Nervioso , Humanos , COVID-19/complicaciones , SARS-CoV-2 , Estrés Oxidativo , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/terapia
11.
Eur J Trauma Emerg Surg ; 49(4): 1891-1896, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37162555

RESUMEN

PURPOSE: The purpose was to analyze our trauma population during two periods to assess for predictors of recidivism. METHODS: Prior (2007-2011, n = 879) and recent (2014-2019, n = 954) orthopaedic trauma patients were reviewed. Recidivists were those returning with an unrelated injury. Recidivism rates were compared, and factors associated with recidivism were identified. RESULTS: Recidivism decreased: 18.7% to 14.3% (p = 0.01). Mean age and sex of the two cohorts were not different. Recent recidivists were more likely to sustain gunshot wound (GSW) injuries (22.1% vs 18.9%, p = 0.09), and mental illness was more common (56.6% vs 28.1%, p < 0.0001). The recent recidivist population was less often married (12.9% vs 23.8%, p = 0.03), and both recidivist groups were often underinsured (Medicaid or uninsured: (60.6% vs 67.0%)). CONCLUSION: Recidivism diminished, although more GSW and mental illness were seen. Recidivists are likely to be underinsured. The changing profile of recidivists may be attributed to socioeconomic trends and new programs to improve outcomes after trauma.


Asunto(s)
Ortopedia , Reincidencia , Heridas por Arma de Fuego , Humanos , Heridas por Arma de Fuego/epidemiología , Puntaje de Gravedad del Traumatismo , Sistema de Registros , Estudios Retrospectivos
12.
ACS Chem Neurosci ; 14(11): 1971-1980, 2023 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-37200505

RESUMEN

Missense mutations along the leucine-rich repeat kinase 2 (LRRK2) protein are a major contributor to Parkinson's Disease (PD), the second most commonly occurring neurodegenerative disorder worldwide. We recently reported the development of allosteric constrained peptide inhibitors that target and downregulate LRRK2 activity through disruption of LRRK2 dimerization. In this study, we designed doubly constrained peptides with the objective of inhibiting C-terminal of Roc (COR)-COR mediated dimerization at the LRRK2 dimer interface. We show that the doubly constrained peptides are cell-permeant, bind wild-type and pathogenic LRRK2, inhibit LRRK2 dimerization and kinase activity, and inhibit LRRK2-mediated neuronal apoptosis, and in contrast to ATP-competitive LRRK2 kinase inhibitors, they do not induce the mislocalization of LRRK2 to skein-like structures in cells. This work highlights the significance of COR-mediated dimerization in LRRK2 activity while also highlighting the use of doubly constrained peptides to stabilize discrete secondary structural folds within a peptide sequence.


Asunto(s)
Péptidos , Proteínas Serina-Treonina Quinasas , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/genética , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/química , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/metabolismo , Dimerización , Leucina/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Péptidos/farmacología , Péptidos/metabolismo , Mutación
13.
Int J Mol Sci ; 24(9)2023 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-37175853

RESUMEN

There is mounting evidence that the development of Alzheimer's disease (AD) interacts extensively with immunological processes in the brain and extends beyond the neuronal compartment. Accumulation of misfolded proteins can activate an innate immune response that releases inflammatory mediators and increases the severity and course of the disease. It is widely known that type-I interferon-driven neuroinflammation in the central nervous system (CNS) accelerates the development of numerous acute and chronic CNS diseases. It is becoming better understood how the cyclic GMP-AMP synthase (cGAS) and its adaptor protein Stimulator of Interferon Genes (STING) triggers type-I IFN-mediated neuroinflammation. We discuss the principal elements of the cGAS-STING signaling pathway and the mechanisms underlying the association between cGAS-STING activity and various AD pathologies. The current understanding of beneficial and harmful cGAS-STING activity in AD and the current treatment pathways being explored will be discussed in this review. The cGAS-STING regulation offers a novel therapeutic opportunity to modulate inflammation in the CNS because it is an upstream regulator of type-I IFNs.


Asunto(s)
Enfermedad de Alzheimer , Interferón Tipo I , Humanos , Inmunidad Innata , Interferón Tipo I/metabolismo , Enfermedades Neuroinflamatorias , Nucleotidiltransferasas/metabolismo , Transducción de Señal/genética
14.
Cell Rep ; 42(5): 112499, 2023 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-37178122

RESUMEN

Physical activity is associated with beneficial adaptations in human and rodent metabolism. We studied over 50 complex traits before and after exercise intervention in middle-aged men and a panel of 100 diverse strains of female mice. Candidate gene analyses in three brain regions, muscle, liver, heart, and adipose tissue of mice indicate genetic drivers of clinically relevant traits, including volitional exercise volume, muscle metabolism, adiposity, and hepatic lipids. Although ∼33% of genes differentially expressed in skeletal muscle following the exercise intervention are similar in mice and humans independent of BMI, responsiveness of adipose tissue to exercise-stimulated weight loss appears controlled by species and underlying genotype. We leveraged genetic diversity to generate prediction models of metabolic trait responsiveness to volitional activity offering a framework for advancing personalized exercise prescription. The human and mouse data are publicly available via a user-friendly Web-based application to enhance data mining and hypothesis development.


Asunto(s)
Adaptación Fisiológica , Transcriptoma , Masculino , Persona de Mediana Edad , Humanos , Femenino , Ratones , Animales , Transcriptoma/genética , Obesidad/metabolismo , Aclimatación , Tejido Adiposo/metabolismo , Músculo Esquelético/metabolismo
15.
Harmful Algae ; 123: 102401, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36894209

RESUMEN

Karenia brevis blooms, also known as red tide, are a recurring problem in the coastal Gulf of Mexico. These blooms have the capacity to inflict substantial damage to human and animal health as well as local economies. Thus, monitoring and detection of K. brevis blooms at all life stages and cell concentrations is essential for ensuring public safety. Current K. brevis monitoring methods have several limitations, including size resolution limits and concentration ranges, limited capacity for spatial and temporal profiling, and/or small sample volume processing. Here, a novel monitoring method wherein an autonomous digital holographic imaging microscope (AUTOHOLO), that overcomes these limitations and can characterize K. brevis concentrations in situ, is presented. Using the AUTOHOLO, in situ field measurements were conducted in the coastal Gulf of Mexico during an active K. brevis bloom over the 2020-21 winter season. Surface and sub-surface water samples collected during these field studies were also analyzed in the lab using benchtop holographic imaging and flow cytometry for validation. A convolutional neural network was trained for automated classification of K. brevis at all concentration ranges. The network was validated with manual counts and flow cytometry, yielding a 90% accuracy across diverse datasets with varying K. brevis concentrations. The usefulness of pairing the AUTOHOLO with a towing system was also demonstrated for characterizing particle abundance over large spatial distances, which could potentially facilitate characterization of spatial distributions of K. brevis during bloom events. Future applications of the AUTOHOLO can include integration into existing HAB monitoring networks to enhance detection capabilities for K. brevis in aquatic environments around the world.


Asunto(s)
Dinoflagelados , Animales , Humanos , Microscopía , Floraciones de Algas Nocivas , Golfo de México , Predicción
16.
Soft Matter ; 19(15): 2726-2736, 2023 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-36974942

RESUMEN

The digital alchemy framework is an extended ensemble simulation technique that incorporates particle attributes as thermodynamic variables, enabling the inverse design of colloidal particles for desired behavior. Here, we extend the digital alchemy framework for the inverse design of patchy spheres that self-assemble into target crystal structures. To constrain the potentials to non-trivial solutions, we conduct digital alchemy simulations with constant second virial coefficient. We optimize the size, range, and strength of patchy interactions in model triblock Janus spheres to self-assemble the 2D kagome and snub square lattices and the 3D pyrochlore lattice, and demonstrate self-assembly of all three target structures with the designed models. The particles designed for the kagome and snub square lattices assemble into high quality clusters of their target structures, while competition from similar polymorphs lower the yield of the pyrochlore assemblies. We find that the alchemically designed potentials do not always match physical intuition, illustrating the ability of the method to find nontrivial solutions to the optimization problem. We identify a window of second virial coefficients that result in self-assembly of the target structures, analogous to the crystallization slot in protein crystallization.

17.
Prog Transplant ; 33(1): 69-77, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36540954

RESUMEN

Purpose: Malignancy after heart transplantation is associated with poor outcomes. At present, no prediction model exists for any malignancy within the first year after transplant. Methods: We studied adults who underwent heart transplantation included in the multicenter, national Scientific Registry of Transplant Recipients from January 2000 through April 2021. Possible predictors of malignancy were identified based on their known association with malignancy. Multiple imputations were conducted for missing values using predictive mean matching. A multivariable logistic regression model for predicting malignancy development within the first year after transplant was developed and internally validated via 500 bootstrapped samples to estimate the optimism-corrected measures of model accuracy and performance. Results: Among the 47 212 recipients comprising 16% females, 76% whites, 7% with prior malignancy, and a median age of 56 years; 865 (2.3% of those with non-missing data) developed malignancy within the first year after transplant. Prior malignancy, older age at heart transplantation, white race, and nonischemic heart failure etiology were the strongest predictors of new malignancy. The optimism-corrected model had modest discrimination (C-statistic: 0.70, 95% CI: 0.69-0.72) and good calibration and performance (calibration slope: 0.96; Cox-Snell R2: 0.063), particularly at lower predicted risk. A nomogram for the practicing clinician was developed. Conclusions: Using selection variables previously linked to cutaneous malignancy, our model was modestly predictive of the development of any malignancy in the first year after heart transplantation. Future research could identify factors that may improve malignancy prediction, including incorporation of time-to-event data.


Asunto(s)
Trasplante de Corazón , Neoplasias , Femenino , Adulto , Humanos , Persona de Mediana Edad , Masculino , Modelos Logísticos , Factores de Riesgo
18.
Injury ; 54(2): 519-524, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36372562

RESUMEN

INTRODUCTION: Recidivism after orthopedic trauma results in greater morbidity and costs. Prior studies explored the effects of social and medical factors affecting the frequency of return to the hospital with new, unrelated injury. Identification of mental, social and other risk factors for trauma recidivism may provide opportunities for mitigation. The purposes of this study are to determine the rates of subsequent, unrelated injury noted among orthopedic trauma patients at a large urban trauma center and to evaluate what patient and injury features are associated with greater rates of trauma recidivism. We hypothesize higher rates of new injuries will be related to ballistic trauma and other forms of assault, alcohol and recreational drug use, unemployment, and unmarried status among our trauma patients. METHODS: A series of 954 skeletally mature patients at a level 1 trauma center over a 5 year period were included in the study. All were treated operatively for thoracolumbar, pelvic ring, acetabulum, and/or proximal or shaft femoral fractures from a high energy mechanism. Retrospective review of demographic, injury, medical, and social factors, and subsequent care was performed. Trauma recidivism was defined as returning to the emergency department for treatment of any new injury. A backward stepwise logistic regression statistical analysis was used to identify independent predictors of recidivism. RESULTS: Mean age of all patients was 41.2 years, and 73.2% were male. 136 patients (14.3%) returned with a new injury within a mean of 21 months. These trauma recidivists were more likely to sustain a GSW (22.1% vs 11.4%, p = 0.001). They had higher rates of substance use, including tobacco (57.4% vs 41.8%, p = 0.001) and recreational drugs (50.7% vs 34.4%, p = 0.001), and were less likely to be married (10% vs 25.9%, p<0.001). Mental illness was pervasive, noted in 56.6% of patients with new injury (vs 32.8%, p<0.001). Medicaid insurance was most common in the trauma recidivist population (58.1% vs 35.0%, p = 0.001), and 12.5% were uninsured. Completing high school or more education was protective (93% non-recidivist (vs 79%, p = 0.001). Sixty-nine patients (50.7%) were repeat trauma recidivists within the study period. Independent predictors of new injury included recreational drug use (OR 1.64, p = 0.05) and history of assault due to GSW or other means (OR 1.67, p = 0.05). History of pre-existing mental illness represented the greatest risk factor for trauma recidivism (OR 2.55, p<0.001). DISCUSSION: New injuries resulting in emergency department presentation after prior orthopedic trauma occurred in 14.3% and were associated with history of assault, lower education, Medicaid insurance, tobacco smoking and recreational drug use. Mental illness was the greatest risk factor. Over half of patients with these additional injuries were repeat trauma recidivists, returning for another new injury within less than 2 years. Awareness of risk factors may promote focused education and other interventions to mitigate this burden. LEVEL OF EVIDENCE: Level 3 retrospective, prognostic.


Asunto(s)
Lesiones de Repetición , Heridas y Lesiones , Humanos , Masculino , Adulto , Femenino , Estudios Retrospectivos , Factores de Riesgo , Centros Traumatológicos , Servicio de Urgencia en Hospital , Pronóstico , Heridas y Lesiones/epidemiología
19.
Health (London) ; 27(6): 1096-1114, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-35674318

RESUMEN

Policy promotes the active participation of those with lived experience of mental health difficulties in UK NHS mental health services, from the level of collaborative care-planning to service delivery, leadership and development. However, research indicates different forms of resistance to the implementation of such service user involvement. This article reports the findings of a qualitative, interview-based study which used Foucauldian discourse analysis and psychoanalytic theory to understand how resistances are produced through the interplay of clinical mental health professionals' subjectivity and their organisational context. Service user involvement was found to highlight conflicts within clinicians' roles. Central to this conflict was an ambivalent relationship to the power associated with these roles. Power could protect professionals from work related stresses, but could also be used to dominate, silence and coerce service users in ways that conflicted with the core function of providing care. Whilst important, raising awareness of such conflict will arouse discomfort and resistance where psychological defences are challenged. A parallel is drawn with psychotherapeutic change, in which resistance must be understood and worked with as part of meaningful change.


Asunto(s)
Servicios de Salud Mental , Medicina Estatal , Humanos , Personal de Salud , Investigación Cualitativa , Salud Mental , Reino Unido
20.
Neurol Res ; 45(10): 877-883, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32758096

RESUMEN

OBJECTIVE: Traumatic spine injuries are a relatively common occurrence and are associated with functional impairment, loss of neurologic function, and spinal deformity. A number of spinal trauma classification systems have been developed with varying degrees of acceptance. This review provides a chronological overview of spinal trauma classification systems, with special consideration towards the benefits and pitfalls related to each. Cervical, thoracolumbar, and sacral trauma classification systems are discussed. METHODS: A review of the literature was performed. Published articles that reported on bony spinal trauma classification systems were examined. No year exemptions were identified. The reference lists of all selected articles were screened for additional studies. Article inclusion and exclusion criteria were defined a priori. RESULTS: A total of 20 classification systems were identified from years 1938-2017. Of these 20 classification systems, 6 were cervical, 11 were thoracolumbar and 3 were sacral. The modernization of bony spinal trauma classification has been characterized by the development of weighted scales that include injury morphology, integrity of associated ligamentous structures and neurologic status. CONCLUSION: For widespread acceptance and adoption in the clinical setting, future spinal trauma scoring classification will need to remain simple, highly reproducible, and impart information with regard to clinical decision-making and prognosis that may be effectively communicated across each medical specialty involved in the care of these patients.


Asunto(s)
Vértebras Lumbares , Traumatismos Vertebrales , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Torácicas/diagnóstico por imagen , Vértebras Torácicas/lesiones , Traumatismos Vertebrales/diagnóstico por imagen
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