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1.
Cureus ; 16(3): e55490, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38571843

RESUMEN

Posterior reversible encephalopathy syndrome (PRES) can be defined as a clinical syndrome of headache, seizures, visual disturbance, altered mental status, and characteristic magnetic resonance imaging (MRI) findings of vasogenic edema in the posterior subcortical parietal-occipital white matter. There are numerous potential inciting factors, including immunosuppression, renal disease, malignancy, cytotoxic medications, hypertension, preeclampsia, and eclampsia. In this paper, we present the case of a 21-year-old female at 19 weeks gestation presenting with symptoms consistent with preeclampsia with severe features and PRES. She was transferred to our facility after initial stabilization. She had an atypical course of preeclampsia prior to 20 weeks gestation, PRES lacking seizure activity, and ultimately her case resulted in intrauterine fetal demise (IUFD) at 20 weeks and six days gestation. As indicated by its name, PRES is considered a fully reversible syndrome, and the patient recovered after stabilization of her hypertensive disorder and delivery of the fetus. This case illustrates the importance of prompt recognition and treatment of hypertensive disorders in pregnant patients and the possibility of complications that can result in significant morbidity and mortality for both the mother and fetus.

2.
Dement Geriatr Cogn Disord ; 53(2): 47-56, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38479371

RESUMEN

INTRODUCTION: Cognitive screening measures are an established part of a dementia assessment and often include measures of subjective difficulties, e.g., Everyday Memory Questionnaire (EMQ), informant-rated difficulty, Cambridge Behavioural Inventory - Revised (CBI-R), and objective cognitive assessments like Addenbrooke's Cognitive Examination (ACE-III). While these measures have validity for the purpose of diagnosing dementia, in clinical practice they are often used outside of their evidence base for the purpose of cognitive re-assessment. The current study sought to evaluate the psychometric properties for the repeated use of these assessments. METHODS: This study used a longitudinal design, which included 49 healthy controls, 33 people with subjective memory difficulties, and 10 people with Alzheimer's disease (AD) being assessed twice, with approximately a 1-year interval between assessments. RESULTS: The EMQ has adequate re-test reliability (r = 0.78), but people with an AD diagnosis rated their memory as better than those with SMD, making it unsuitable as a measure. The CBI-R had moderate re-test reliability (r = 0.62). However, deterioration on the CBI-R was not useful for diagnosing AD. The ACE-III has high re-test reliability (r = 0.89). A change of five was associated with reasonable classification accuracy for identifying AD and achieved statistical significance. CONCLUSION: Using a 1-year interval, of the three measures used in this study, only the ACE-III total score may be a useful measure of change over time, although it should be applied cautiously due to the lack of representativeness of the sample, and change scores should always be triangulated with other forms of evidence of deterioration.


Asunto(s)
Enfermedad de Alzheimer , Demencia , Pruebas Neuropsicológicas , Psicometría , Humanos , Masculino , Femenino , Anciano , Reproducibilidad de los Resultados , Demencia/diagnóstico , Estudios Longitudinales , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/psicología , Anciano de 80 o más Años , Encuestas y Cuestionarios , Persona de Mediana Edad , Trastornos de la Memoria/diagnóstico , Pruebas de Estado Mental y Demencia
3.
bioRxiv ; 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38260581

RESUMEN

Optimizing behavioral strategy requires belief updating based on new evidence, a process that engages higher cognition. In schizophrenia, aberrant belief dynamics may lead to psychosis, but the mechanisms underlying this process are unknown, in part, due to lack of appropriate animal models and behavior readouts. Here, we address this challenge by taking two synergistic approaches. First, we generate a mouse model bearing patient-derived point mutation in Grin2a (Grin2aY700X+/-), a gene that confers high-risk for schizophrenia and recently identified by large-scale exome sequencing. Second, we develop a computationally trackable foraging task, in which mice form and update belief-driven strategies in a dynamic environment. We found that Grin2aY700X+/- mice perform less optimally than their wild-type (WT) littermates, showing unstable behavioral states and a slower belief update rate. Using functional ultrasound imaging, we identified the mediodorsal (MD) thalamus as hypofunctional in Grin2aY700X+/- mice, and in vivo task recordings showed that MD neurons encoded dynamic values and behavioral states in WT mice. Optogenetic inhibition of MD neurons in WT mice phenocopied Grin2aY700X+/- mice, and enhancing MD activity rescued task deficits in Grin2aY700X+/- mice. Together, our study identifies the MD thalamus as a key node for schizophrenia-relevant cognitive dysfunction, and a potential target for future therapeutics.

4.
Cureus ; 15(11): e49067, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38125223

RESUMEN

Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/coronavirus disease 2019 (COVID-19) pneumonia can have a range of clinical presentations ranging from being asymptomatic to having severe acute respiratory syndrome (SARS). Autoimmune hemolytic anemia (AIHA) is a very rare presentation of COVID-19. We present the case of a 67-year-old male with a past medical history of chronic obstructive pulmonary disease (COPD) who presented to the emergency department (ED) with shortness of breath and was found to be COVID-19-positive. His laboratory results demonstrated autoimmune hemolytic anemia with decreased hemoglobin (Hgb), elevated lactate dehydrogenase (LDH), decreased haptoglobin, peripheral smear showing spherocytes, and a positive direct antiglobulin (Coombs) test. The patient was started on glucocorticoids, but his hemoglobin continued to worsen. The dose of glucocorticoids was increased significantly, and his hemoglobin started improving with the resolution of hemolysis. Autoimmune hemolytic anemia is usually treated with glucocorticoids, but escalating glucocorticoid doses increases the risk of side effects. This case report highlights the importance of further research needed to establish guidelines for AIHA in the context of COVID-19 pneumonia.

5.
Artículo en Inglés | MEDLINE | ID: mdl-37983153

RESUMEN

This manuscript proposes an electrical definition of therapeutic dose for spinal-cord systems used for the treatment of chronic pain, analogous to the pharmacological definition. Dose-response relationships are fundamental to pharmacology, radio-therapy, and other treatments, but have never been properly established for neuromodulation. This manuscript offers a robust measure of dose, pre-requisite to establishing a reliable and repeatable dose-response relationship. The new definition, enabled by the system transresistance obtained from measurement of evoked action potentials, recognizes the mechanism of action of spinal cord stimulation (SCS), and should improve acceptance of the therapy as compared to pharmacological treatments which are currently used more frequently for the treatment of chronic pain. The new definition suggests methods for personalization and standardization of the dose in SCS, and is potentially generalizable to all neuromodulation therapies in which nervous tissue is excited including sacral nerve stimulation (SNS), vagal nerve stimulation (VNS) and deep-brain stimulation (DBS). Formulas are provided, and applied using patient data. Powerful conclusions are drawn from application of the new measure.


Asunto(s)
Dolor Crónico , Estimulación de la Médula Espinal , Humanos , Estimulación de la Médula Espinal/métodos , Médula Espinal/fisiología , Potenciales Evocados , Estimulación Eléctrica
6.
Leuk Res Rep ; 20: 100391, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37711672

RESUMEN

Ophthalmic and neurologic involvement are rare complications of CLL, with few cases reported in the literature. We report a case of CLL with leukemic infiltration of the optic nerve and review of literature focusing on management and outcomes. A patient with heavily pretreated CLL presented to our hospital with progressive eye pain and was found to have infiltrative optic neuritis. CSF analysis confirmed involvement with CLL. After systemic treatment with R-CHOP and high-dose methotrexate, along with intrathecal cytarabine and hydrocortisone, she experienced significant improvement and was discharged home. Given the rarity of ophthalmic involvement in CLL, we reviewed all 15 previously reported cases of CLL with optic neuropathy as the first manifestation of CNS involvement and discussed the range of treatment options used and their respective outcomes.

7.
Med Educ Online ; 28(1): 2241182, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37519051

RESUMEN

Undergraduate medical learners from historically marginalized groups face significant barriers, which was made concrete at our institution when a student presented her research indicating that Black students felt unsure about which faculty members to approach. To better support our students, we used Kern's model for curriculum development and a critical pedagogy approach to create a Faculty Allyship Curriculum (FAC). A total of 790 individuals attended 90 workshops across 16 months and 20 individuals have completed the FAC. A majority of participants reported they felt at least moderately confident in their ability to teach learners who are underrepresented in medicine, mentor learners who are different than they are, and teach allyship topics. An informal content analysis of open-ended responses indicated changes in awareness, attitude, insight, and use of language and being more likely to display advocacy. For others considering creating a similar program, partnering with an existing program allows for rapid implementation and reach to a wide audience. We also recommend: beginning with a coalition of willing learners to quickly build community and culture change; ensuring that the curriculum supports ongoing personal commitment and change for the learners; and supporting facilitators in modeling imperfection and upstanding, 'calling in' rather than 'calling out' learners.


Asunto(s)
Curriculum , Diversidad, Equidad e Inclusión , Docentes Médicos , Estudiantes , Humanos , Mentores , Estudiantes/psicología
8.
Thromb Res ; 228: 10-20, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37263122

RESUMEN

INTRODUCTION: Tissue factor expression on monocytes is implicated in the pathophysiology of sepsis-induced coagulopathy. How tissue factor is expressed by monocyte subsets (classical, intermediate and non-classical) is unknown. METHODS: Monocytic tissue factor surface expression was investigated during three conditions. Primary human monocytes and microvascular endothelial cell co-cultures were used for in vitro studies. Volunteers received a bolus of lipopolysaccharide (2 ng/kg) to induce endotoxemia. Patients with sepsis, or controls with critical illness unrelated to sepsis, were recruited from four intensive care units. RESULTS: Contact with endothelium and stimulation with lipopolysaccharide reduced the proportion of intermediate monocytes. Lipopolysaccharide increased tissue factor surface expression on classical and non-classical monocytes. Endotoxemia induced profound, transient monocytopenia, along with activation of coagulation pathways. In the remaining circulating monocytes, tissue factor was up-regulated in intermediate monocytes, though approximately 60 % of individuals (responders) up-regulated tissue factor across all monocyte subsets. In critically ill patients, tissue factor expression on intermediate and non-classical monocytes was significantly higher in patients with established sepsis than among non-septic patients. Upon recovery of sepsis, expression of tissue factor increased significantly in classical monocytes. CONCLUSION: Tissue factor expression in monocyte subsets varies significantly during health, endotoxemia and sepsis.


Asunto(s)
Endotoxemia , Sepsis , Humanos , Monocitos/metabolismo , Endotoxemia/complicaciones , Tromboplastina/metabolismo , Tromboinflamación , Lipopolisacáridos
9.
Adv Nutr ; 14(5): 948-958, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37270030

RESUMEN

Achieving optimal health is an aspirational goal for the population, yet the definition of health remains unclear. The role of nutrition in health has evolved beyond correcting malnutrition and specific deficiencies and has begun to focus more on achieving and maintaining 'optimal' health through nutrition. As such, the Council for Responsible Nutrition held its October 2022 Science in Session conference to advance this concept. Here, we summarize and discuss the findings of their Optimizing Health through Nutrition - Opportunities and Challenges workshop, including several gaps that need to be addressed to advance progress in the field. Defining and evaluating various indices of optimal health will require overcoming these key gaps. For example, there is a strong need to develop better biomarkers of nutrient status, including more accurate markers of food intake, as well as biomarkers of optimal health that account for maintaining resilience-the ability to recover from or respond to stressors without loss to physical and cognitive performance. In addition, there is a need to identify factors that drive individualized responses to nutrition, including genotype, metabotypes, and the gut microbiome, and to realize the opportunity of precision nutrition for optimal health. This review outlines hallmarks of resilience, provides current examples of nutritional factors to optimize cognitive and performance resilience, and gives an overview of various genetic, metabolic, and microbiome determinants of individualized responses.


Asunto(s)
Microbioma Gastrointestinal , Ciencias de la Nutrición , Humanos , Estado Nutricional , Biomarcadores
10.
Dement Geriatr Cogn Disord ; 52(4): 195-204, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37271132

RESUMEN

INTRODUCTION: Visual and spatial perception (VSP) are cognitive domains frequently assessed in the screening and neuropsychological assessment of dementia. Evidence suggests that VSP impairment is common in the early stages of Alzheimer's disease (AD). Despite this evidence, the ability of VSP tests to discriminate between healthy older adults and people with AD remains mixed. The purpose of this literature review was to employ a systematic search strategy to identify empirical evidence supporting the diagnostic utility of VSP tests which may be used in the screening and diagnosis of AD. METHODS: Specified criteria were used to perform a systematic literature search of the PsycINFO and PubMed databases with no date restrictions. Relevant data from the selected studies were extracted, and a published appraisal tool (the Quality Assessment of Diagnostic Accuracy Studies-2) was used to evaluate methodological quality. RESULTS: Of the 144 articles returned, six studies and 11 VSP tests met review inclusion criteria. Four tests demonstrated both sensitivity and specificity values above 80%. A computerised 3D Visual Task demonstrated the highest sensitivity and specificity values (90% and 95%, respectively). The quality of the identified studies was considered to be satisfactory. Identified limitations and the implications of issues relating to study methodology are discussed, and recommendations for future research are suggested. CONCLUSION: The evidence from this review suggests that certain tests of VSP may be a useful addition to the routine screening of AD.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Demencia , Humanos , Anciano , Enfermedad de Alzheimer/diagnóstico , Demencia/diagnóstico , Disfunción Cognitiva/diagnóstico , Pruebas Neuropsicológicas , Percepción , Sensibilidad y Especificidad
11.
J Nutr Educ Behav ; 55(5): 331-342, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37164549

RESUMEN

OBJECTIVE: Identify factors influencing eating behaviors among emerging adults in the military. DESIGN: Focused ethnography using interviews, observations, and artifacts for data. SETTING: Three US Naval installations. PARTICIPANTS: Thirty-two active-duty Sailors aged 18-25 years. ANALYSIS: Qualitative data were organized in NVivo and analyzed sequentially to categorize culturally relevant domains and themes using a social ecological model (SEM). Descriptive statistics were used to describe questionnaire data in SPSS (version 27.0, IBM, 2020). RESULTS: Leaders encouraged healthy eating through policies and messages, but cultural contradictions and environmental barriers undermined Sailors' efforts to eat healthily. Stress and resource constraints (intrapersonal), peer pressure (social), unhealthy food environments and lack of access to food preparation (environmental), and eating on the go because of mission-first norms (cultural) promoted unhealthy eating behaviors. Nutrition and culinary literacy (intrapersonal); peer support and leadership engagement (social); access to healthy, convenient, and low-cost foods (environmental); and indoctrination to healthy eating during recruit training (cultural) positively influenced eating behaviors. CONCLUSION AND IMPLICATIONS: The eating behaviors of service members are influenced by many modifiable factors. Targeted education, leadership engagement, and policies that make nutritious foods easily accessible, appealing, and preferred are needed.


Asunto(s)
Personal Militar , Humanos , Adulto , Adolescente , Adulto Joven , Conducta Alimentaria , Estado Nutricional , Dieta Saludable
12.
Rev Sci Instrum ; 94(5)2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-37204284

RESUMEN

A hyperbaric aerodynamic levitator has been developed for containerless materials research at specimen temperatures exceeding 2000 °C and pressures up to 10.3 MPa (1500 psi). This report describes the prototype instrument design and observations of the influence of specimen size, density, pressure, and flow rate on levitation behavior. The effect of pressure on heat transfer was also assessed by studying the heating and cooling behavior of levitated Al2O3 liquids. A threefold increase in the convective heat transfer coefficient was estimated as pressure increased to 10.3 MPa. The results demonstrate that hyperbaric aerodynamic levitation is a promising technique for containerless materials research at high gas pressures.

13.
Nano Lett ; 23(11): 4785-4792, 2023 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-37220025

RESUMEN

While the performance of metal halide perovskite light-emitting diodes (PeLEDs) has rapidly improved in recent years, their stability remains a bottleneck to commercial realization. Here, we show that the thermal stability of polymer hole-transport layers (HTLs) used in PeLEDs represents an important factor influencing the external quantum efficiency (EQE) roll-off and device lifetime. We demonstrate a reduced EQE roll-off, a higher breakdown current density of approximately 6 A cm-2, a maximum radiance of 760 W sr-1 m-2, and a longer device lifetime for PeLEDs using polymer HTLs with high glass-transition temperatures. Furthermore, for devices driven by nanosecond electrical pulses, a record high radiance of 1.23 MW sr-1 m-2 and an EQE of approximately 1.92% at 14.6 kA cm-2 are achieved. Thermally stable polymer HTLs enable stable operation of PeLEDs that can sustain more than 11.7 million electrical pulses at 1 kA cm-2 before device failure.

14.
Sci Rep ; 13(1): 5950, 2023 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-37045858

RESUMEN

Employing a methodology reported in a recent theoretical study on male astronauts, this study estimated the effects of body size and aerobic countermeasure (CM) exercise in a four-person, all-female crew composed of individuals drawn from a stature range (1.50- to 1.90-m) representative of current space agency requirements (which exist for stature, but not for body mass) upon total energy expenditure (TEE), oxygen (O2) consumption, carbon dioxide (CO2) and metabolic heat (Hprod) production, and water requirements for hydration, during space exploration missions. Assuming geometric similarity across the stature range, estimates were derived using available female astronaut data (mean age: 40-years; BMI: 22.7-kg·m-2; resting VO2 and VO2max: 3.3- and 40.5-mL·kg-1·min-1) on 30- and 1080-day missions, without and with, ISS-like countermeasure exercise (modelled as 2 × 30-min aerobic exercise at 75% VO2max, 6-day·week-1). Where spaceflight-specific data/equations were not available, terrestrial equivalents were used. Body size alone increased 24-h TEE (+ 30%), O2 consumption (+ 60%), CO2 (+ 60%) and Hprod (+ 60%) production, and water requirements (+ 17%). With CM exercise, the increases were + 25-31%, + 29%, + 32%, + 38% and + 17-25% across the stature range. Compared to the previous study of theoretical male astronauts, the effect of body size on TEE was markedly less in females, and, at equivalent statures, all parameter estimates were lower for females, with relative differences ranging from -5% to -29%. When compared at the 50th percentile for stature for US females and males, these differences increased to - 11% to - 41% and translated to larger reductions in TEE, O2 and water requirements, and less CO2 and Hprod during 1080-day missions using CM exercise. Differences between female and male theoretical astronauts result from lower resting and exercising O2 requirements (based on available astronaut data) of female astronauts, who are lighter than male astronauts at equivalent statures and have lower relative VO2max values. These data, combined with the current move towards smaller diameter space habitat modules, point to a number of potential advantages of all-female crews during future human space exploration missions.


Asunto(s)
Dióxido de Carbono , Vuelo Espacial , Humanos , Masculino , Femenino , Adulto , Citocromo P-450 CYP2B1 , Astronautas , Ejercicio Físico , Tamaño Corporal , Oxígeno , Agua
15.
Nutrients ; 15(5)2023 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-36904203

RESUMEN

Optimal nutrition is imperative for psychological health. Oxidative stress and inflammation are underlying etiologies for alterations in psychological health. Warfighters are at risk of health concerns such as depression due to increased stress in austere environments and family separation while deployed. Over the last decade, research has demonstrated the health benefits of flavonoids found in fruits and berries. Berry flavonoids have potent antioxidant and anti-inflammatory properties by inhibiting oxidative stress and inflammation. In this review, the promising effects of various berries rich in bioactive flavonoids are examined. By inhibiting oxidative stress, berry flavonoids have the potential to modulate brain, cardiovascular, and intestinal health. There is a critical need for targeted interventions to address psychological health concerns within the warfighter population, and a berry flavonoid-rich diet and/or berry flavonoid dietary supplement intervention may prove beneficial as an adjunctive therapy. Structured searches of the literature were performed in the PubMed, CINAHL, and EMBASE databases using predetermined keywords. This review focuses on berry flavonoids' critical and fundamental bioactive properties and their potential effects on psychological health in investigations utilizing cell, animal, and human model systems.


Asunto(s)
Dieta , Flavonoides , Animales , Humanos , Flavonoides/farmacología , Frutas , Antioxidantes/farmacología , Inflamación
16.
BMJ Mil Health ; 2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36792226

RESUMEN

The role of nutrition and performance is well established. Service members' physical and cognitive performance, sleep and mood are impacted by nutritional choices. Although many eating patterns have emerged, consensus among experts recommend a dietary pattern focused on predominantly whole plant-based foods. Adequate intakes of fruits, vegetables, whole grains, beans, legumes, nuts and seeds should be prioritised. Implementation of strategic and intentional fuelling strategies around times of activity maintain adequate energy stores, enhance recovery and protect against training injuries. Carbohydrates are prioritised before, during and after activity or a mission, although the type and amount will vary based on duration and intensity of activity. Protein is generally the focus after activity or a mission and may be included before activity depending on individual tolerance. There are no specific recommendations for fat consumption before, during and after exercise that will improve performance. That said, Service members generally tolerate low-fat meals/snacks prior to exercise, limit fat intake during exercise, may include fat as part of the post exercise meal/snack, and generally consume most fat during the maintenance and growth phase. Careful consideration and planning for food and fluid requirements should be made when Service members are exposed to heat, cold and/or altitude. Operational rations are formulated to meet the nutritional needs of all Service members across a variety of diverse climates, environments and altitudes. Service members may use dietary supplements to improve their performance and need to be aware of available resources to help them make informed decisions.

17.
J Spec Oper Med ; 23(1): 88-91, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36827684

RESUMEN

Full-spectrum Human Performance Optimization (HPO) is essential for Special Operations Forces (SOF). Adequate hydration is essential to all aspects of performance (physical and cognitive) and recovery. Water losses occur as a result of physical activity and can increase further depending on clothing and environmental conditions. Without intentional and appropriate strategic hydration planning, Operators are at increased risk for degradation in performance and exertional heat illness. The purpose of this article is to highlight current best practices for maintaining hydration before, during, and after activity, while considering various environmental conditions. Effective leadership and planning are necessary for preparing Operators for successful military operations.


Asunto(s)
Personal Militar , Humanos , Personal Militar/psicología , Ejercicio Físico , Liderazgo
18.
Thorax ; 78(10): 1019-1027, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-36808087

RESUMEN

BACKGROUND: Tracheostomies in children are associated with significant morbidity, poor quality of life, excess healthcare costs and excess mortality. The underlying mechanisms facilitating adverse respiratory outcomes in tracheostomised children are poorly understood. We aimed to characterise airway host defence in tracheostomised children using serial molecular analyses. METHODS: Tracheal aspirates, tracheal cytology brushings and nasal swabs were prospectively collected from children with a tracheostomy and controls. Transcriptomic, proteomic and metabolomic methods were applied to characterise the impact of tracheostomy on host immune response and the airway microbiome. RESULTS: Children followed up serially from the time of tracheostomy up to 3 months postprocedure (n=9) were studied. A further cohort of children with a long-term tracheostomy were also enrolled (n=24). Controls (n=13) comprised children without a tracheostomy undergoing bronchoscopy. Long-term tracheostomy was associated with airway neutrophilic inflammation, superoxide production and evidence of proteolysis when compared with controls. Reduced airway microbial diversity was established pre-tracheostomy and sustained thereafter. CONCLUSIONS: Long-term childhood tracheostomy is associated with a inflammatory tracheal phenotype characterised by neutrophilic inflammation and the ongoing presence of potential respiratory pathogens. These findings suggest neutrophil recruitment and activation as potential exploratory targets in seeking to prevent recurrent airway complications in this vulnerable group of patients.


Asunto(s)
Proteómica , Traqueostomía , Niño , Humanos , Traqueostomía/efectos adversos , Calidad de Vida , Tráquea , Inflamación/etiología
19.
Cell Mol Life Sci ; 80(1): 35, 2023 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-36622452

RESUMEN

Chemokine CXCL8 is a key facilitator of the human host immune response, mediating neutrophil migration, and activation at the site of infection and injury. The oxidative burst is an important effector mechanism which leads to the generation of reactive nitrogen species (RNS), including peroxynitrite. The current study was performed to determine the potential for nitration to alter the biological properties of CXCL8 and its detection in human disease. Here, we show peroxynitrite nitrates CXCL8 and thereby regulates neutrophil migration and activation. The nitrated chemokine was unable to induce transendothelial neutrophil migration in vitro and failed to promote leukocyte recruitment in vivo. This reduced activity is due to impairment in both G protein-coupled receptor signaling and glycosaminoglycan binding. Using a novel antibody, nitrated CXCL8 was detected in bronchoalveolar lavage samples from patients with pneumonia. These findings were validated by mass spectrometry. Our results provide the first direct evidence of chemokine nitration in human pathophysiology and suggest a natural mechanism that limits acute inflammation.


Asunto(s)
Interleucina-8 , Ácido Peroxinitroso , Humanos , Quimiocinas/metabolismo , Inflamación/metabolismo , Interleucina-8/metabolismo , Interleucina-8/farmacología , Leucocitos/metabolismo , Neutrófilos , Ácido Peroxinitroso/farmacología
20.
Neuroimage Clin ; 37: 103328, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36696808

RESUMEN

BACKGROUND: Aging and dementia involve the disruption of brain molecular pathways leading to the alterations in tissue composition and gross morphology of the brain. Phenotypic and biomarker overlap between various etiologies of dementia supports a need for new modes of information to more accurately distinguish these disorders. Brain mechanical properties, which can be measured noninvasively by MR elastography, represent one understudied feature that are sensitive to neurodegenerative processes. In this study, we used two stiffness estimation schemes to test the hypothesis that different etiologies of dementia are associated with unique patterns of mechanical alterations across the cerebral cortex. METHODS: MR elastography data were acquired for six clinical groups including amyloid-negative cognitively unimpaired (CU), amyloid-positive cognitively unimpaired (A + CU), amyloid-positive participants with mild cognitive impairment (A + MCI), amyloid-positive participants with Alzheimer's clinical syndrome (A + ACS), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). Stiffness maps were computed using two neural network inversions with the objective to at least partially separate the parenchyma-specific and morphological effects of neurodegeneration on mechanical property estimates. A tissue-confined inversion algorithm was designed to obtain the best estimate of stiffness in the brain parenchyma itself, while a regionally-aware inversion algorithm was used to measure the tissue stiffness along with the surroundings. Mean stiffness of 15 bilateral gray matter cortical regions were considered for statistical analysis. First, we tested the hypothesis that cortical stiffness changes in the aging brain. Next, we tested the overall study hypothesis by first comparing stiffness in each clinical group to the CU group, and then comparing the clinical groups against one another. Finally, we assessed the spatial and statistical overlap between atrophy and stiffness changes for both inversions. RESULTS: Cortical brain regions become softer with age for both inversions with larger effects observed using regionally-aware stiffness. Stiffness decreases in the range 0.010-0.027 kPa per year were observed. Pairwise comparisons of each clinical group with cognitively unimpaired participants demonstrated 5 statistically significant differences in stiffness for tissue-confined measurements and 19 statistically different stiffness changes for the regionally-aware stiffness measurements. Pairwise comparisons between clinical groups further demonstrated unique patterns of stiffness differences. Analysis of the atrophy-versus-stiffness relationship showed that regionally-aware stiffness measurements exhibit higher sensitivity to neurodegeneration with findings that are not fully explained by partial volume effects or atrophy. CONCLUSIONS: Both tissue-confined and regionally-aware stiffness estimates exhibited unique and complementary stiffness differences in various etiologies of dementia. Our results suggest that mechanical alterations measured by MRE reflect both tissue-specific differences as well as environmental effects. Multi-inversion schemes in MRE may provide new insights into the relationships between neuropathology and brain biomechanics.


Asunto(s)
Enfermedad de Alzheimer , Diagnóstico por Imagen de Elasticidad , Demencia Frontotemporal , Humanos , Diagnóstico por Imagen de Elasticidad/métodos , Demencia Frontotemporal/patología , Corteza Cerebral/patología , Atrofia/patología , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/patología , Imagen por Resonancia Magnética/métodos
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