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1.
Mol Neurobiol ; 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39313656

RESUMEN

The abuse of synthetic steroids, such as nandrolone decanoate (ND), is often associated with violent behavior, increasing the risk of traumatic brain injury (TBI). After a TBI, proteins like APP, ß-amyloid peptide-42 (Aß42), and phosphorylated tau (pTau) accumulate and trigger endoplasmic reticulum (ER) stress associated with an unfolded protein response (UPR). The involvement of mitochondrial bioenergetics in this context remains unexplored. We interrogate whether the abuse of ND before TBI alters the responses of ER stress and mitochondrial bioenergetics in connection with neurodegeneration and memory processing in mice. Male CF1 adult mice were administered ND (15 mg/kg) or vehicle (VEH) s.c. for 19 days, coinciding with the peak day of aggressive behavior, and then underwent cortical controlled impact (CCI) or sham surgery. Spatial memory was assessed through the Morris water maze task (MWM) post-TBI. In synaptosome preparations, i) we challenged mitochondrial complexes (I, II, and V) in a respirometry assay, employing metabolic substrates, an uncoupler, and inhibitors; and ii) assessed molecular biomarkers through Western blot. TBI significantly increased APP, Aß42, and pTauSer396 levels, along with ER-stress proteins, GRP78, ATF6, and CHOP, implying it primed apoptotic signaling. Concurrently, TBI reduced mitochondrial Ca2+ efflux in exchange with Na+, disturbed the formation/dissipation of membrane potential, increased H2O2 production, decreased biogenesis (PGC-1⍺ and TOM20), and ATP biosynthesis coupled with oxygen consumption. Unexpectedly, ND abuse before TBI attenuated the elevations in APP, Aß42, and pTauSer396, accompanied by a decrease in GRP78, ATF6, and CHOP levels, and partial normalization of mitochondrial-related endpoints. A principal component analysis revealed a key hierarchical signature featuring mitochondrial Ca2+ efflux, CHOP, GRP78, TOM20, H2O2, and bioenergetic efficiency as a unique variable (PC1) able to explain the memory deficits caused by TBI, as well as the preservation of memory fitness induced by prior ND abuse.

2.
Chem Commun (Camb) ; 60(81): 11532-11535, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39310982

RESUMEN

The synthesis and characterization of the first examples of cubane containing interlocked molecules are reported. Catenanes and rotaxanes have been prepared by hydrogen bond templation with cubane-1,3-dicarboxamides replacing isophthalamide motifs.

3.
Glob Chang Biol ; 30(7): e17412, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39044634

RESUMEN

The hadopelagic environment remains highly understudied due to the inherent difficulties in sampling at these depths. The use of sediment environmental DNA (eDNA) can overcome some of these restrictions as settled and preserved DNA represent an archive of the biological communities. We use sediment eDNA to assess changes in the community within one of the world's most productive open-ocean ecosystems: the Atacama Trench. The ecosystems around the Atacama Trench have been intensively fished and are affected by climate oscillations, but the understanding of potential impacts on the marine community is limited. We sampled five sites using sediment cores at water depths from 2400 to ~8000 m. The chronologies of the sedimentary record were determined using 210Pbex. Environmental DNA was extracted from core slices and metabarcoding was used to identify the eukaryote community using two separate primer pairs for different sections of the 18S rRNA gene (V9 and V7) effectively targeting pelagic taxa. The reconstructed communities were similar among markers and mainly composed of chordates and members of the Chromista kingdom. Alpha diversity was estimated for all sites in intervals of 15 years (from 1842 to 2018), showing a severe drop in biodiversity from 1970 to 1985 that aligns with one of the strongest known El Niño events and extensive fishing efforts during the time. We find a direct impact of sea surface temperature on the community composition over time. Fish and cnidarian read abundance was examined separately to determine whether fishing had a direct impact, but no direct relation was found. These results demonstrate that sediment eDNA can be a valuable emerging tool providing insight in historical perspectives on ecosystem developments. This study constitutes an important step toward an improved understanding of the importance of environmental and anthropogenic drivers in affecting open and deep ocean communities.


Asunto(s)
Biodiversidad , ADN Ambiental , Ecosistema , Sedimentos Geológicos , ARN Ribosómico 18S , Sedimentos Geológicos/análisis , ADN Ambiental/análisis , ARN Ribosómico 18S/genética , Chile , Animales , Código de Barras del ADN Taxonómico , Eucariontes/genética , Organismos Acuáticos/genética
4.
Plant Physiol ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38918899

RESUMEN

Population expansion is a global issue, especially for food production. Meanwhile, global climate change is damaging our soils, making it difficult for crops to thrive and lowering both production and quality. Poor nutrition and salinity stress affect plant growth and development. Although the impact of individual plant stresses has been studied for decades, the real stress scenario is more complex due to the exposure to multiple stresses at the same time. Here we investigate using existing evidence and a meta-analysis approach to determine molecular linkages between two contemporaneous abiotic stimuli, phosphate (Pi) deficiency and salinity, on a single plant cell model, the root hairs (RHs), which is the first plant cell exposed to them. Understanding how these two stresses work molecularly in RHs may help us build super-adaptable crops and sustainable agriculture in the face of global climate change.

5.
J Pediatr ; 272: 114099, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38754775

RESUMEN

OBJECTIVE: To increase the percentage of patients who undergo rapid magnetic resonance imaging (rMRI) rather than computed tomography (CT) for evaluation of mild traumatic brain injury (TBI) from 45% in 2020 to 80% by December 2021. STUDY DESIGN: This was a quality improvement initiative targeted to patients presenting to the pediatric emergency department presenting with mild TBI, with baseline data collected from January 2020 to December 2020. From January 2021 to August 2021, we implemented a series of improvement interventions and tracked the percentage of patients undergoing neuroimaging who received rMRI as their initial study. Balancing measures included proportion of all patients with mild TBI who underwent neuroimaging of any kind, proportion of patients requiring sedation, emergency department length of stay, and percentage with clinically important TBI. RESULTS: The utilization of rMRI increased from a baseline of 45% to a mean of 92% in the intervention period. Overall neuroimaging rates did not change significantly after the intervention (19.8 vs 23.2%, P = .24). There was no difference in need for anxiolysis (12 vs 7%, P = .30) though emergency department length of stay was marginally increased (1.4 vs 1.7 hours, P = < 0.01). CONCLUSION: In this quality improvement initiative, transition to rMRI as the primary imaging modality for the evaluation of minor TBI was achieved at a level 1 pediatric trauma center with no significant increase in overall use of neuroimaging.


Asunto(s)
Servicio de Urgencia en Hospital , Traumatismos Cerrados de la Cabeza , Imagen por Resonancia Magnética , Mejoramiento de la Calidad , Humanos , Imagen por Resonancia Magnética/métodos , Niño , Masculino , Femenino , Traumatismos Cerrados de la Cabeza/diagnóstico por imagen , Adolescente , Preescolar , Tomografía Computarizada por Rayos X/métodos , Neuroimagen/métodos , Conmoción Encefálica/diagnóstico por imagen , Tiempo de Internación/estadística & datos numéricos , Estudios Retrospectivos
6.
Neural Regen Res ; 19(12): 2673-2683, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38595286

RESUMEN

Regenerative approaches towards neuronal loss following traumatic brain or spinal cord injury have long been considered a dogma in neuroscience and remain a cutting-edge area of research. This is reflected in a large disparity between the number of studies investigating primary and secondary injury as therapeutic targets in spinal cord and traumatic brain injuries. Significant advances in biotechnology may have the potential to reshape the current state-of-the-art and bring focus to primary injury neurotrauma research. Recent studies using neural-glial factor/antigen 2 (NG2) cells indicate that they may differentiate into neurons even in the developed brain. As these cells show great potential to play a regenerative role, studies have been conducted to test various manipulations in neurotrauma models aimed at eliciting a neurogenic response from them. In the present study, we systematically reviewed the experimental protocols and findings described in the scientific literature, which were peer-reviewed original research articles (1) describing preclinical experimental studies, (2) investigating NG2 cells, (3) associated with neurogenesis and neurotrauma, and (4) in vitro and/or in vivo, available in PubMed/MEDLINE, Web of Science or SCOPUS, from 1998 to 2022. Here, we have reviewed a total of 1504 papers, and summarized findings that ultimately suggest that NG2 cells possess an inducible neurogenic potential in animal models and in vitro. We also discriminate findings of NG2 neurogenesis promoted by different pharmacological and genetic approaches over functional and biochemical outcomes of traumatic brain injury and spinal cord injury models, and provide mounting evidence for the potential benefits of manipulated NG2 cell ex vivo transplantation in primary injury treatment. These findings indicate the feasibility of NG2 cell neurogenesis strategies and add new players in the development of therapeutic alternatives for neurotrauma.

7.
Biol Lett ; 20(2): 20230480, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38412964

RESUMEN

Active electroreception-the ability to detect objects and communicate with conspecifics via the detection and generation of electric organ discharges (EODs)-has evolved convergently in several fish lineages. South American electric fishes (Gymnotiformes) are a highly species-rich group, possibly in part due to evolution of an electric organ (EO) that can produce diverse EODs. Neofunctionalization of a voltage-gated sodium channel gene accompanied the evolution of electrogenic tissue from muscle and resulted in a novel gene (scn4aa) uniquely expressed in the EO. Here, we investigate the link between variation in scn4aa and differences in EOD waveform. We combine gymnotiform scn4aa sequences encoding the C-terminus of the Nav1.4a protein, with biogeographic data and EOD recordings to test whether physiological transitions among EOD types accompany differential selection pressures on scn4aa. We found positive selection on scn4aa coincided with shifts in EOD types. Species that evolved in the absence of predators, which likely selected for reduced EOD complexity, exhibited increased scn4aa evolutionary rates. We model mutations in the protein that may underlie changes in protein function and discuss our findings in the context of gymnotiform signalling ecology. Together, this work sheds light on the selective forces underpinning major evolutionary transitions in electric signal production.


Asunto(s)
Pez Eléctrico , Animales , Pez Eléctrico/genética , Órgano Eléctrico/fisiología , Filogenia , Canales de Sodio/genética , América del Sur
9.
Exp Neurol ; 363: 114352, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36813223

RESUMEN

Decreasing neurotrophic support and impaired mitochondrial bioenergetics are key mechanisms for long-term neurodegeneration and cognitive decline after traumatic brain injury (TBI). We hypothesize that preconditioning with lower and higher volumes of physical exercise upregulates the CREB-BDNF axis and bioenergetic capability, which might serve as neural reserves against cognitive impairment after severe TBI. Using a running wheel mounted in the home cage, mice were engaged in lower (LV, 48 h free access, and 48 h locked) and higher (HV, daily free access) exercise volumes for thirty days. Subsequently, LV and HV mice remained for additional thirty days in the home cage with the running wheel locked and were euthanized. The sedentary group had the running wheel always locked. For the same type of exercise stimulus in a given time, daily workout presents higher volume than alternate days workout. The total distance ran in the wheel was the reference parameter to confirm distinct exercise volumes. On average, LV exercise ran 27.522 m and HV exercise ran 52.076 m. Primarily, we investigate whether LV and HV protocols increase neurotrophic and bioenergetic support in the hippocampus thirty days after exercise ceased. Regardless of volume, exercise increased hippocampal pCREBSer133-CREB-proBDNF-BDNF signaling and mitochondrial coupling efficiency, excess capacity, and leak control, that may compose the neurobiological basis for neural reserves. Further, we challenge these neural reserves against secondary memory deficits triggered by a severe TBI. After thirty days of exercise LV and HV, and sedentary (SED) mice were submitted to the CCI model. Mice remained for additional thirty days in the home cage with the running wheel locked. The mortality after severe TBI was approximately 20% in LV and HV, while in the SED was 40%. Also, LV and HV exercise sustained hippocampal pCREBSer133-CREB-proBDNF-BDNF signaling, mitochondrial coupling efficiency, excess capacity, and leak control for thirty days after severe TBI. Corroborating these benefits, the mitochondrial H2O2 production linked to complexes I and II was attenuated by exercise regardless of the volume. These adaptations attenuated spatial learning and memory deficits caused by TBI. In summary, preconditioning with LV and HV exercise builds up long-lasting CREB-BDNF and bioenergetic neural reserves that preserve memory fitness after severe TBI.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Reserva Cognitiva , Condicionamiento Físico Animal , Ratones , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Peróxido de Hidrógeno , Condicionamiento Físico Animal/fisiología , Hipocampo/metabolismo , Trastornos de la Memoria/etiología , Lesiones Traumáticas del Encéfalo/complicaciones
10.
Pesqui. vet. bras ; 43: e07161, 2023. tab, ilus
Artículo en Inglés | VETINDEX | ID: biblio-1422296

RESUMEN

Iron deficiency anemia (IDA) in humans is defined as the decrease of total hemoglobin concentration and the non-production of the adult hemoglobin subtype 2 - HbA2 (α2δ2 chains), which is considered a marker of IDA severity in humans, dosed together with the iron serum. This study aimed to determine the standard of hemoglobin types in piglets induced to experimentally IDA in the first 21 days of life (delivery to weaning). In the present study, 40 piglets born from four naïve gilts, were randomly and equally assigned among the gilts. On the third day after delivery, the groups were randomly distributed in different environments (cement and clay floors) and according to the iron supplementation (iron dextran and placebo). Erythrocyte parameters, serum iron, and hemoglobin trait were analyzed at four moments between birth and weaning days. The group of piglets that did not receive iron dextran supplementation on the third-day post-birth and were placed in the pen without soil did not present HbA2 from the seventh day onwards on the agarose electrophoretogram (pH 8.6) and this observation was correlated to decrease of serum iron (ρ: 0.156, p=0.003) when compared to the other groups' piglets that did not present iron deficiency. In the present study was possible to determine the swine hemoglobin pattern in IDA, since HbA2 was absent in piglets with IDA in comparison to the non-ferropenic groups and the correlation between the reduction of iron levels and the absence of HbA2.


A anemia por deficiência de ferro (ADF) em humanos é definida como a diminuição da concentração de hemoglobina total e a não produção da hemoglobina adulta subtipo 2 - HbA2 (cadeias α2δ2), que é considerada um marcador de gravidade de IDA em humanos, dosado em conjunto com o soro de ferro. Este estudo teve como objetivo determinar o padrão dos tipos de hemoglobina em leitões induzidos experimentalmente à IDA nos primeiros 21 dias de vida (parto ao desmame). Quarenta leitões, nascidos de quatro marrãs nulíparas, foram distribuídos aleatoriamente e igualmente entre as leitoas. No terceiro dia após o parto, os grupos foram distribuídos aleatoriamente em diferentes ambientes (piso de cimento e barro) e de acordo com a suplementação de ferro (ferro dextrano e placebo). Parâmetros eritrocitários, ferro sérico e traço de hemoglobina foram analisados em quatro momentos, entre o nascimento e o desmame. O grupo de leitões que não recebeu suplementação de ferro dextrano no terceiro dia pós-parto e foi colocado em baia sem solo não apresentou HbA2 a partir do sétimo dia no eletroforetograma de agarose (pH 8,6) e esta observação foi correlacionada com diminuição da concentração sérica ferro (ρ: 0,156, p=0,003) quando comparados aos demais grupos leitões que não apresentavam deficiência de ferro. No presente estudo foi possível determinar o padrão hemoglobinêmico suíno na IDA, uma vez que, a HbA2 estava ausente nos leitões com ADF em comparação aos grupos não ferropênicos e há correlação entre a redução dos níveis de ferro e a ausência de HbA2.


Asunto(s)
Animales , Recién Nacido , Hemoglobinas/análisis , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/inducido químicamente , Anemia Ferropénica/prevención & control , Anemia Ferropénica/veterinaria , Sus scrofa , Hemoglobinopatías/veterinaria , Enfermedades de los Porcinos , Electroforesis de las Proteínas Sanguíneas/veterinaria , Deficiencias de Hierro/veterinaria
11.
Elife ; 112022 12 09.
Artículo en Inglés | MEDLINE | ID: mdl-36484778

RESUMEN

RNA interference is an ancient mechanism with many regulatory roles in eukaryotic genomes, with small RNAs acting as their functional element. While there is a wide array of classes of small-RNA-producing loci, those resulting from stem-loop structures (hairpins) have received profuse attention. Such is the case of microRNAs (miRNAs), which have distinct roles in plants and animals. Fungi also produce small RNAs, and several publications have identified miRNAs and miRNA-like (mi/milRNA) hairpin RNAs in diverse fungal species using deep sequencing technologies. Despite this relevant source of information, relatively little is known about mi/milRNA features in fungi, mostly due to a lack of established criteria for their annotation. To systematically assess mi/milRNA characteristics and annotation confidence, we searched for publications describing mi/milRNA loci and re-assessed the annotations for 41 fungal species. We extracted and normalized the annotation data for 1727 reported mi/milRNA loci and determined their abundance profiles, concluding that less than half of the reported loci passed basic standards used for hairpin RNA discovery. We found that fungal mi/milRNA are generally more similar in size to animal miRNAs and were frequently associated with protein-coding genes. The compiled genomic analyses identified 25 mi/milRNA loci conserved in multiple species. Our pipeline allowed us to build a general hierarchy of locus quality, identifying more than 150 loci with high-quality annotations. We provide a centralized annotation of identified mi/milRNA hairpin RNAs in fungi which will serve as a resource for future research and advance in understanding the characteristics and functions of mi/milRNAs in fungal organisms.


Asunto(s)
MicroARNs , ARN de Hongos , Animales , ARN de Hongos/genética , ARN de Hongos/química , Regulación Fúngica de la Expresión Génica , MicroARNs/genética , Interferencia de ARN , Hongos/genética
12.
JCO Oncol Pract ; 18(12): 826-827, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36219814
13.
Mitochondrion ; 66: 7-12, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35843591

RESUMEN

Antibiotics may trigger alterations in mitochondrial function, which has been explored in cells culture, and in animal model of sepsis. This study sought to evaluate whether antibiotic therapy affects mitochondrial bioenergetics in a 68-patients clinical study. We studied mitochondrial respiratory rates at two time points: the first day of antibiotic administration and three days after. The Δbasal, ΔCI, ΔCII respiration, and ΔBCE respiratory rates were not different between patients administered with polymyxin, vancomycin, amoxicillin-clavulanate, and azithromycin compared to those who were not administered. Specific beta-lactams are associated with specific modifications in mitochondrial respiratory endpoints - patients who used meropenem had higher delta C2 values compared to those who did not (p = 0.03). Patients who used piperacillin-tazobactam had lower delta C1 (p = 0.03) values than those who did not, but higher delta C2 values (p = 0.02). These mitochondrial metabolic signatures in isolated lymphocytes challenges the proposed effects of antibiotics in mitochondrial bioenergetics of cell cultures, but at current status have an uncertain clinical significance.


Asunto(s)
Choque Séptico , Amoxicilina/uso terapéutico , Antibacterianos , Azitromicina/uso terapéutico , Ácido Clavulánico/uso terapéutico , Metabolismo Energético , Humanos , Linfocitos , Meropenem/uso terapéutico , Mitocondrias , Combinación Piperacilina y Tazobactam/uso terapéutico , Polimixinas/uso terapéutico , Estudios Prospectivos , Choque Séptico/tratamiento farmacológico , Vancomicina/uso terapéutico , beta-Lactamas/uso terapéutico
14.
J Neurosurg Pediatr ; : 1-13, 2022 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-35426814

RESUMEN

OBJECTIVE: The aim of this study was to determine differences in complications and outcomes between posterior fossa decompression with duraplasty (PFDD) and without duraplasty (PFD) for the treatment of pediatric Chiari malformation type I (CM1) and syringomyelia (SM). METHODS: The authors used retrospective and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM1-SM who received PFD or PFDD and had at least 1 year of follow-up data. Preoperative, treatment, and postoperative characteristics were recorded and compared between groups. RESULTS: A total of 692 patients met the inclusion criteria for this database study. PFD was performed in 117 (16.9%) and PFDD in 575 (83.1%) patients. The mean age at surgery was 9.86 years, and the mean follow-up time was 2.73 years. There were no significant differences in presenting signs or symptoms between groups, although the preoperative syrinx size was smaller in the PFD group. The PFD group had a shorter mean operating room time (p < 0.0001), fewer patients with > 50 mL of blood loss (p = 0.04), and shorter hospital stays (p = 0.0001). There were 4 intraoperative complications, all within the PFDD group (0.7%, p > 0.99). Patients undergoing PFDD had a 6-month complication rate of 24.3%, compared with 13.7% in the PFD group (p = 0.01). There were no differences between groups for postoperative complications beyond 6 months (p = 0.33). PFD patients were more likely to require revision surgery (17.9% vs 8.3%, p = 0.002). PFDD was associated with greater improvements in headaches (89.6% vs 80.8%, p = 0.04) and back pain (86.5% vs 59.1%, p = 0.01). There were no differences between groups for improvement in neurological examination findings. PFDD was associated with greater reduction in anteroposterior syrinx size (43.7% vs 26.9%, p = 0.0001) and syrinx length (18.9% vs 5.6%, p = 0.04) compared with PFD. CONCLUSIONS: PFD was associated with reduced operative time and blood loss, shorter hospital stays, and fewer postoperative complications within 6 months. However, PFDD was associated with better symptom improvement and reduction in syrinx size and lower rates of revision decompression. The two surgeries have low intraoperative complication rates and comparable complication rates beyond 6 months.

15.
JCO Oncol Pract ; 18(7): e1132-e1140, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35394806

RESUMEN

PURPOSE: Prostate cancer is the most common cancer among men in the United States. The majority of prostate cancer treatment occurs in the ambulatory setting, and patients and their caregivers take on significant responsibility for monitoring and managing treatment and disease-related toxicity. Digital health coaching has shown promise as a tool to positively influence outcomes. We completed a single-arm pilot study to assess the feasibility of digital health coaching in men with prostate cancer. METHODS: Men with a history of prostate cancer requiring treatment in the past 2 years were eligible for inclusion. Participants engaged in a 12-week health coaching program, consisting of a combination of at least one telephone call and up to four digital nudges (defined as content delivered via text, e-mail, or app on the basis of the participant's preference) per week. Prostate cancer-specific content addressed one of the following topics each week: fatigue, pain management, healthy eating, exercise, managing incontinence, sexual health, managing stress and anxiety, financial toxicity, goal setting during treatment, managing side effects, communicating with the health care team, and medication adherence. Services were provided at no cost to the participant. RESULTS: A hundred patients were consented for the study, and 88 enrolled. The feasibility threshold of 60% was met with 63 of the 88 enrolled individuals completing the 3-month program (proportion = 71.6%; 90% CI, 62.6 to 79.4; P = .016). CONCLUSION: Digital health coaching for men with prostate cancer is feasible. These findings support further evaluation of digital health coaching for men with prostate cancer in larger randomized controlled trials.


Asunto(s)
Tutoría , Neoplasias de la Próstata , Ansiedad , Estudios de Factibilidad , Humanos , Masculino , Proyectos Piloto , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/terapia , Estados Unidos
16.
J Neurochem ; 161(2): 173-186, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35157328

RESUMEN

Severe traumatic brain injury (TBI) is associated with high rates of mortality and long-term disability linked to neurochemical abnormalities. Although purine derivatives play important roles in TBI pathogenesis in preclinical models, little is known about potential changes in purine levels and their implications in human TBI. We assessed cerebrospinal fluid (CSF) levels of purines in severe TBI patients as potential biomarkers that predict mortality and long-term dysfunction. This was a cross-sectional study performed in 17 severe TBI patients (Glasgow Coma Scale <8) and 51 controls. Two to 4 h after admission to ICU, patients were submitted to ventricular drainage and CSF collection for quantification of adenine and guanine purine derivatives by HPLC. TBI patients' survival was followed up to 3 days from admission. A neurofunctional assessment was performed through the modified Rankin Scale (mRS) 2 years after ICU admission. Purine levels were compared between control and TBI patients, and between surviving and non-surviving patients. Relative to controls, TBI patients presented increased CSF levels of GDP, guanosine, adenosine, inosine, hypoxanthine, and xanthine. Further, GTP, GDP, IMP, and xanthine levels were different between surviving and non-surviving patients. Among the purines, guanosine was associated with improved mRS (p = 0.042; r = -0.506). Remarkably, GTP displayed predictive value (AUC = 0.841, p = 0.024) for discriminating survival versus non-survival patients up to 3 days from admission. These results support TBI-specific purine signatures, suggesting GTP as a promising biomarker of mortality and guanosine as an indicator of long-term functional disability.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Biomarcadores/líquido cefalorraquídeo , Lesiones Traumáticas del Encéfalo/diagnóstico , Estudios Transversales , Escala de Coma de Glasgow , Guanosina , Guanosina Trifosfato , Humanos , Purinas , Xantina
17.
JCO Oncol Pract ; 18(3): e360-e371, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34807752

RESUMEN

PURPOSE: The purpose of this study was to develop the Oncology Opportunity Cost Assessment Tool (OOCAT), a survey instrument to evaluate the opportunity costs patients experience when seeking medical oncology care. METHODS: Development of the OOCAT involved extensive patient engagement through both focus groups and interviews. First, the study team developed a list of opportunity cost concepts, which included patients' logistical and financial considerations related to seeking care. We conducted focus groups with patients to expand upon this list of concepts, and then developed a set of questions that incorporated all the concepts generated during the focus groups. To refine these questions, we next performed cognitive interviews with another set of patients to ensure content validity and clarity of instrument items, refining the OOCAT iteratively on the basis of feedback. RESULTS: We engaged 23 participants (17 patients and six caregivers) across four focus groups and 17 participants in cognitive interviews. Focus group participants generated 112 concepts, which resulted in an initial OOCAT with 16 questions. Cognitive interviews resulted in modification of 12 questions and addition of two questions (related to coordination of transportation and impact on home responsibilities). The final OOCAT consisted of 18 items examining time requirements for appointments, financial implications of traveling to appointments for the patient and the caregiver, and logistical and quality-of-life challenges associated with traveling for appointments. CONCLUSION: We developed the OOCAT, an instrument designed to evaluate patient-level opportunity costs of seeking medical oncology care. Further studies to validate the OOCAT are underway.


Asunto(s)
Cuidadores , Calidad de Vida , Cuidadores/psicología , Humanos , Oncología Médica , Calidad de Vida/psicología , Encuestas y Cuestionarios
18.
JCO Oncol Pract ; 18(4): e610-e619, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34678074

RESUMEN

PURPOSE: The COVID-19 pandemic necessitated a rapid expansion of telehealth use in oncology, a specialty in which prior utilization was low in part because of barriers perceived by providers. Understanding the changing perceptions of medical oncology providers during the pandemic is critical for continued expansion and improvement of telehealth in cancer care. This study was designed to identify medical oncology providers' perceptions of telehealth video visits as influenced by the COVID-19 pandemic. METHODS: We conducted semi-structured interviews with medical oncology providers from November 20, 2020, to January 27, 2021, at the Sidney Kimmel Cancer Center at Thomas Jefferson University, a National Cancer Institute-designated cancer center in an urban, academic health system in Philadelphia, PA. We assessed provider perceptions of the impact of the COVID-19 pandemic on (1) provider-level comfort and willingness for telehealth, (2) provider-perceived patient comfort and willingness to engage in telehealth, and (3) continued barriers to successful telehealth use. RESULTS: Volunteer and convenience sampling resulted in the participation of 25 medical oncology providers, including 18 physicians and seven advanced practice providers, in semi-structured interviews. Of the 25 participants, 13 (52%) were female and 19 (76%) were White, with an average age of 48.5 years (standard deviation = 12.6). Respondents largely stated an increased comfort level and willingness for use of video visits. In addition, respondents perceived a positive change in patient comfort and willingness, mostly driven by convenience, accessibility, and reduced risk of COVID-19 exposure. However, several reported technologic issues and limited physical examination capability as remaining barriers to telehealth adoption. CONCLUSION: The rapid adoption of telehealth necessitated by the COVID-19 pandemic has increased provider-level and provider-perceived patient comfort and willingness to engage in video visits for cancer care. As both providers and patients increasingly accept telehealth across many use cases, future work should focus on further addressing technology and physical examination barriers and ensuring continued reimbursement for telehealth as a routine part of covered care.


Asunto(s)
COVID-19 , Médicos , Telemedicina , COVID-19/epidemiología , Femenino , Humanos , Oncología Médica , Persona de Mediana Edad , Pandemias
19.
Artículo en Inglés | MEDLINE | ID: mdl-34589662

RESUMEN

PURPOSE: Germline testing (GT) for prostate cancer (PCA) is now central to treatment and hereditary cancer assessment. With rising demand for and shortage of genetic counseling (GC), tools to deliver pretest informed consent across practice settings are needed to improve access to GT and precision care. Here, we report on Evaluation and Management for Prostate Oncology, Wellness, and Risk (EMPOWER), a patient-choice study for pretest video-based genetic education (VBGE) versus GC to inform urgent practice needs. PATIENTS AND METHODS: Men with PCA or at risk for PCA (family history of PCA) were eligible and could choose pretest VBGE or GC. Outcomes included decisional conflict for GT, change in genetics knowledge, satisfaction, and intention to share results with family and/or providers. Descriptive statistics summarized results with counts and percentages for categorical variables and mean ± standard deviation for continuous variables. Data were compared with Fisher's exact, chi-squared, or Wilcoxon two-sample tests. Mean change in genetics knowledge was compared with t tests. The significance level was set a priori at .05. RESULTS: Data on the first 127 participants were analyzed. Characteristics were White (85.8%), bachelor's degree (66.9%), and PCA diagnosis (90.6%). The majority chose VBGE (71%) versus GC (29%; P < .001). No differences were observed in decisional conflict for GT or satisfaction. Cancer genetics knowledge improved in both groups without significant difference (+0.9 VBGE, +1.8 GC, P = .056). Men who chose VBGE had higher intention to share GT results (96.4% VBGE v 86.4% GC, P = .02). Both groups had high rates of GT uptake (VBGE 94.4%, GC 92%). CONCLUSION: A substantial proportion of men opted for pretest VBGE, with comparable patient-reported outcomes and uptake of GT. The results support the use of pretest video to address the critical GC shortage in the precision era.


Asunto(s)
Conducta de Elección , Educación del Paciente como Asunto/normas , Neoplasias de la Próstata/diagnóstico , Anciano , Distribución de Chi-Cuadrado , Asesoramiento Genético/métodos , Asesoramiento Genético/psicología , Asesoramiento Genético/normas , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto/métodos , Neoplasias de la Próstata/genética , Encuestas y Cuestionarios
20.
JCO Oncol Pract ; 17(9): e1333-e1343, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34288697

RESUMEN

PURPOSE: Telehealth in medical oncology has expanded secondary to the COVID-19 pandemic. However, quantitative research on medical oncology telehealth use shows conflicting results on patient satisfaction, whereas qualitative data are sparse. Our qualitative study aimed to identify the factors influencing patient acceptability of video visits for medical oncology care before and at the onset of the expansion of telehealth because of the COVID-19 pandemic. METHODS: Semi-structured interviews were conducted between November 2019 and April 2020 with 20 patients who participated in a telehealth visit with a medical oncology provider at Thomas Jefferson University. RESULTS: Of the 20 participants, 13 (65%) were female and 15 (75%) were White, with a mean (standard deviation) age of 60.5 years (11.8). Patients identified convenience, anxiety, COVID-19, and provider preference as positively influencing the acceptability of video visits; however, some patients noted limitations in provider connection, physical examinations, and visit length as disadvantages. Regarding receipt of serious or bad news, some preferred video visits for privacy, immediacy of results, news processing, and family comfort. Others preferred in-person encounters for provider support and the ability to receive written information and in-person referrals. CONCLUSION: Patient-perceived factors influencing general acceptability, appropriateness of serious and bad news delivery, and future uses of telehealth were unique to each individual, but shared common themes. Understanding each patient's perspective of telehealth acceptability and tailoring use to their preferences is critical for continued utilization. Further research is needed to understand and address reasons for lack of telehealth uptake among certain patients.


Asunto(s)
COVID-19 , Neoplasias , Telemedicina , Femenino , Humanos , Oncología Médica , Persona de Mediana Edad , Neoplasias/terapia , Pandemias , Percepción , SARS-CoV-2
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