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1.
Adv Tech Stand Neurosurg ; 53: 93-118, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39287805

RESUMEN

Ependymomas are the third most common intracranial tumor in children, presenting in both the supratentorial and infratentorial compartments. They may present in infants, young children, and adolescents with symptoms depending on size, location, and the age of the patient. The ideal imaging for evaluation and treatment is MRI. This is crucial for preoperative evaluation and planning, as well as postoperative assessment and evaluating the efficacy of treatment. Essentially without exception, aggressive surgery aimed at complete resection is the initial and most important factor in the long-term outcome of all these children. Histopathologic diagnosis for intracranial pediatric ependymoma has been narrowed to grade II and grade III, no longer characterized as classic and anaplastic. Subsequent conformal photon or proton beam irradiation is an established post-surgical therapy, with solid evidence that it benefits survival and offers lower toxicity to the normal brain of the young child. Although chemotherapeutic treatment has not been generally impactful, immunotherapeutic interventions may be on the horizon. Updated molecular subgrouping of ependymoma is changing the post-resection approach of these tumors with regard to both treatment and outcome. Excluding spinal ependymoma and subependymoma, there are four subtypes that are defined by genetic characteristics, two found in the supratentorial compartment, ST-EPN-YAP1 and ST-EPN-ZFTA, and two in the posterior fossa, PF-EPN-A and PF-EPN-B. Younger children harboring ZFTA fusion-positive supratentorial and type A posterior fossa tumors, regardless of histology, tend toward the poorest outcomes. On the contrary, older children with supratentorial YAP1 fusion-positive ependymomas and type B posterior fossa tumors may survive with surgery alone. The paradigm shift regarding the behavior of the various childhood ependymoma subtypes will hopefully lead to targeted, individualized therapies and improved outcomes.


Asunto(s)
Ependimoma , Neoplasias Infratentoriales , Neoplasias Supratentoriales , Humanos , Ependimoma/terapia , Ependimoma/diagnóstico , Ependimoma/patología , Neoplasias Infratentoriales/terapia , Neoplasias Infratentoriales/patología , Neoplasias Supratentoriales/terapia , Neoplasias Supratentoriales/patología , Neoplasias Supratentoriales/diagnóstico , Niño , Adolescente
2.
J Spine Surg ; 10(2): 244-254, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38974486

RESUMEN

Background: In upright standing, spinopelvic mismatch is compensated by hip extension. However, few studies have investigated the reciprocal relationship between the sagittal alignment of the hip joints and spinopelvic mismatch during upright standing in humans. Our study aims to investigate (I) the relationship between spinopelvic mismatch and hip extension and (II) whether insufficient hip extension against spinopelvic mismatch, i.e., pelvic incidence (PI)-lumbar lordosis (LL), affects trunk inclination in upright standing. Methods: This study was a retrospective cross-sectional study. We included 398 consecutive female patients treated for osteoporosis at our outpatient department between November 2017 and June 2022. Patients with any of the following were excluded from the study: (I) those whose plain whole-spine radiographs did not cover the femurs, (II) those with fractures in the vertebrae or lower extremities, (III) those with a history of surgery of the spine or of the lower extremities, (IV) those with scoliosis with a Cobb angle ≥10° in the anteroposterior radiograph, and (V) those with transitional vertebrae. Sixty-two patients were divided into normal and malalignment groups based on their sagittal spinal alignment. The patients underwent plain whole-spine radiography as a routine examination. A linear approximation between the pelvic femoral angle (PFA), representing hip extension, and PI-LL was obtained in both groups. The optimal PFA of each patient was obtained by substituting the PI-LL into the linear approximation of the normal group. The difference between the optimal and measured PFA was defined as the ΔPFA for each patient. The correlation between the ΔPFA and sagittal vertical axis (SVA) was evaluated in both groups. Results: The PFA and PI-LL were correlated in both groups. The malalignment group had a significantly greater ΔPFA than the normal group. ΔPFA was correlated with SVA only in the malalignment group. Conclusions: The magnitude of the ΔPFA indicated insufficient hip extension to compensate for the spinopelvic mismatch during upright standing.

3.
Front Public Health ; 12: 1346682, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39005986

RESUMEN

Introduction: The COVID-19 pandemic exacerbated mental health concerns and stress among American Indians and Alaska Natives (AI/ANs) in the United States, as well as among frontline workers responding to the pandemic. Psychological First Aid (PFA) is a promising intervention to support mental wellbeing and coping skills during and after traumatic events, such as the COVID-19 pandemic. Since PFA is often implemented rapidly in the wake of a disaster or traumatic event, evidence evaluating its impact is lacking. This paper reports pilot evaluation results from a culturally adapted PFA training designed to support COVID-19 frontline workers and the AI/AN communities they serve during the pandemic. Methods: This study was designed and implemented in partnership with a collaborative work group of public health experts and frontline workers in AI/AN communities. We conducted a pre-post, online pilot evaluation of a culturally adapted online PFA training with COVID-19 frontline workers serving AI/AN communities. Participants completed a baseline survey and two follow-up surveys 1 week and 3 months after completing the PFA training. Surveys included demographic questions and measures of anxiety, burnout, stress, positive mental health, communal mastery, coping skills, PFA knowledge, confidence in PFA skills, and satisfaction with the PFA training. Results: Participants included N = 56 COVID-19 frontline workers in AI/AN communities, 75% were AI/AN, 87% were female, and most (82%) were between the ages of 30-59. Participants reported high satisfaction with the training and knowledge of PFA skills. Pilot results showed significant increases in positive mental health and social wellbeing and reductions in burnout from baseline to 3 months after completing the PFA training among frontline workers. There were no changes in communal mastery, coping skills, stress, or anxiety symptoms during the study period. Discussion: To our knowledge, this is the first pilot evaluation of a PFA training designed and culturally adapted with and for AI/AN communities. Given that many AI/AN communities were disproportionately impacted by COVID-19 and prior mental health inequities, addressing acute and chronic stress is of crucial importance. Addressing traumatic stress through culturally adapted interventions, including Indigenous PFA, is crucial to advancing holistic wellbeing for AI/AN communities.


Asunto(s)
Adaptación Psicológica , Nativos Alasqueños , COVID-19 , Humanos , COVID-19/psicología , Proyectos Piloto , Femenino , Masculino , Nativos Alasqueños/psicología , Adulto , Persona de Mediana Edad , Indígenas Norteamericanos/psicología , Estados Unidos , Primeros Auxilios , Salud Mental , SARS-CoV-2 , Encuestas y Cuestionarios , Personal de Salud/educación , Personal de Salud/psicología , Estrés Psicológico/psicología
4.
Cell ; 187(18): 4926-4945.e22, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38986619

RESUMEN

Posterior fossa group A (PFA) ependymoma is a lethal brain cancer diagnosed in infants and young children. The lack of driver events in the PFA linear genome led us to search its 3D genome for characteristic features. Here, we reconstructed 3D genomes from diverse childhood tumor types and uncovered a global topology in PFA that is highly reminiscent of stem and progenitor cells in a variety of human tissues. A remarkable feature exclusively present in PFA are type B ultra long-range interactions in PFAs (TULIPs), regions separated by great distances along the linear genome that interact with each other in the 3D nuclear space with surprising strength. TULIPs occur in all PFA samples and recur at predictable genomic coordinates, and their formation is induced by expression of EZHIP. The universality of TULIPs across PFA samples suggests a conservation of molecular principles that could be exploited therapeutically.


Asunto(s)
Ependimoma , Ependimoma/genética , Humanos , Neoplasias Infratentoriales/genética , Neoplasias Infratentoriales/patología , Genoma Humano , Lactante , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Niño , Masculino , Femenino
5.
Int J Biol Macromol ; 274(Pt 1): 133177, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38885855

RESUMEN

Under nitrogen deficient conditions, the Aurantiochytrium limacinum strain BL10 greatly increases the production of docosahexaenoic acid (DHA) and n-6 docosapentaenoic acid. Researchers have yet to elucidate the mechanism by which BL10 promotes the activity of polyunsaturated fatty acid synthase (Pfa), which plays a key role in the synthesis of polyunsaturated fatty acid (PUFA). Analysis in the current study revealed that in nitrogen-depleted environments, BL10 boosts the transcription and synthesis of proteins by facilitating the expression of pfa genes via transcriptional regulation. It was also determined that BL10 adjusts the lengths of the 5'- and 3'-untranslated regions (suggesting post-transcriptional regulation) and modifies the ratio of two Pfa1 isoforms to favor PUFA production via post-translational regulation (ubiquitination). These findings clarify the exceptional DHA production of BL10 and provide additional insights into the regulatory mechanisms of PUFA biosynthesis in Aurantiochytrium.


Asunto(s)
Ácido Graso Sintasas , Ácidos Grasos Insaturados , Nitrógeno , Estramenopilos , Nitrógeno/metabolismo , Ácido Graso Sintasas/genética , Ácido Graso Sintasas/metabolismo , Ácidos Grasos Insaturados/biosíntesis , Ácidos Grasos Insaturados/metabolismo , Estramenopilos/genética , Estramenopilos/enzimología , Procesamiento Proteico-Postraduccional , Transcripción Genética , Ácidos Docosahexaenoicos/biosíntesis , Ácidos Docosahexaenoicos/metabolismo
6.
Anal Bioanal Chem ; 416(18): 4207-4218, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38822822

RESUMEN

Mass spectrometry imaging (MSI) platforms such as infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) are advantageous for a variety of applications, including elucidating the localization of neurotransmitters (NTs) and related molecules with respect to ion abundance across a sample without the need for derivatization or organic matrix application. While IR-MALDESI-MSI conventionally uses a thin exogenous ice matrix to improve signal abundance, it has been previously determined that sucrose embedding without the ice matrix improves detection of lipid species in striatal, coronal mouse brain sections. This work considers components of this workflow to determine the optimal sample preparation and matrix to enhance the detection of NTs and their related metabolites in coronal sections from the striatal region of the mouse brain. The discoveries herein will enable more comprehensive follow-on studies for the investigation of NTs to enrich biological pathways and interpretation related to neurodegenerative diseases and ischemic stroke.


Asunto(s)
Encéfalo , Neurotransmisores , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Animales , Neurotransmisores/análisis , Neurotransmisores/metabolismo , Ratones , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Encéfalo/metabolismo , Ratones Endogámicos C57BL , Química Encefálica
7.
Bioelectrochemistry ; 158: 108726, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38733722

RESUMEN

Mucus hypersecretion resulting from excessive proliferation and metaplasia of goblet cells in the airways is the pathological foundation for Chronic obstructive pulmonary disease (COPD). Clinical trials have confirmed the clinical efficacy of pulsed electric field ablation (PFA) for COPD, but its underlying mechanisms is poorly understood. Cellular and animal models of COPD (rich in goblet cells) were established in this study to detect goblet cells' sensitivity to PFA. Schwan's equation was adopted to calculate the cells' transmembrane potential and the electroporation areas in the cell membrane. We found that goblet cells are more sensitive to low-intensity PFA (250 V/cm-500 V/cm) than BEAS-2B cells. It is attributed to the larger size of goblet cells, which allows a stronger transmembrane potential formation under the same electric field strength. Additionally, the transmembrane potential of larger-sized cells can reach the cell membrane electroporation threshold in more areas. Trypan blue staining confirmed that the cells underwent IRE rate was higher in goblet cells than in BEAS-2B cells. Animal experiments also confirmed that the airway epithelium of COPD is more sensitive to PFA. We conclude that lower-intensity PFA can selectively kill goblet cells in the COPD airway epithelium, ultimately achieving the therapeutic effect of treating COPD.


Asunto(s)
Electroporación , Células Caliciformes , Enfermedad Pulmonar Obstructiva Crónica , Células Caliciformes/patología , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/terapia , Animales , Humanos , Electroporación/métodos , Línea Celular , Potenciales de la Membrana , Masculino , Técnicas de Ablación/métodos , Electricidad , Ratones
9.
Arthroplast Today ; 26: 101335, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38440287

RESUMEN

Background: Patellofemoral arthroplasty (PFA) is a treatment option for isolated patellofemoral arthritis. Custom PFA is an innovative procedure utilizing patient-specific instrumentation. The purpose of this study is to evaluate short-term functional outcomes and complications of the custom PFA in treatment of isolated patellofemoral arthritis. Methods: A retrospective study was conducted to analyze patients who received a PFA operation from a single surgeon. Inclusion criteria were surgical patients from 2012 to 2018 who underwent PFA using a custom prosthesis implant. Knee injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS, JR) and Lower Extremity Functional Scale (LEFS) were collected before and after surgery. Results: A total of 79 patients (94 knees) participated in the study; 55 (69.6%) were women. The median age was 57 at the time of index arthroplasty; 15 patients (30 knees) were bilateral. Follow-up rate was 94%. Median follow-up duration was 3.6 years (2-8.9). Overall prefunctional and postfunctional scores differed significantly for both KOOS, JR and LEFS. Postoperative scores increased for KOOS, JR by 27.5 points, and for LEFS, they increased 26.0 points; P < .001 for both. Complications included 6 reoperations (6.7%) related to PFA: 4 conversions (4.4%) to total knee arthroplasty at a median of 2.5 (1.5-3) years after the index procedure, one vastus medialis oblique advancement (1.1%) secondary to patellar maltracking, and one manipulation under anesthesia (1.1%). Conclusions: Custom PFA in patients with isolated patellofemoral arthritis showed good short-term functional outcomes and low revision rates with very few complications.

10.
Int J Cardiol ; 407: 131985, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38513736

RESUMEN

Radiofrequency ablation (RFA) has been a central therapeutic strategy for ventricular tachycardia (VT). However, concerns about its long-term effectiveness and complications have arisen. Pulsed field ablation (PFA), characterized by its nonthermal, highly tissue-selective ablation technique, has emerged as a promising alternative. This comprehensive review delves into the potential advantages and opportunities presented by PFA in the realm of VT, drawing insights from both animal experimentation and clinical case studies. PFA shows promise in generating superior lesions within scarred myocardial tissue, and its inherent repetition dependency holds the potential to enhance therapeutic outcomes. Clinical cases underscore the promise of PFA for VT ablation. Despite its promising applications, challenges such as catheter maneuverability and proarrhythmic effects require further investigation. Large-scale, long-term studies are essential to establish the suitability of PFA for VT treatment.


Asunto(s)
Ablación por Catéter , Taquicardia Ventricular , Taquicardia Ventricular/cirugía , Taquicardia Ventricular/fisiopatología , Taquicardia Ventricular/terapia , Humanos , Ablación por Catéter/métodos , Animales , Resultado del Tratamiento
11.
Europace ; 26(3)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38385529

RESUMEN

AIMS: Pulmonary vein isolation (PVI) is a well-established strategy for the treatment of paroxysmal atrial fibrillation (PAF). Despite randomized controlled trials and real-world data showing the promise of pulsed-field ablation (PFA) for this treatment, long-term efficacy and safety data demonstrating single-procedure outcomes off antiarrhythmic drugs remain limited. The aim of the FARA-Freedom Study was to evaluate the long-term efficacy and safety of PFA using the pentaspline catheter for PAF. METHODS AND RESULTS: FARA-Freedom, a prospective, non-randomized, multicentre study, enrolled patients with PAF undergoing de novo PVI with PFA, who were followed for 12 months with weekly transtelephonic monitoring and a 72-h Holter ECG at 6 and 12 months. The primary safety endpoint was a composite of device- or procedure-related serious adverse events out to 7 days post-ablation and PV stenosis or atrioesophageal (AE) fistula out to 12 months. Treatment success is a composite of acute PVI and chronic success, which includes freedom from any documented atrial tachyarrhythmia longer than 30 s, use of antiarrhythmic drugs or cardioversion after a 3-month blanking period, or use of amiodarone or repeat ablation at any time. The study enrolled 179 PAF patients (62 ± 10 years, 39% female) at 13 centres. At the index procedure, all PVs were successfully isolated with the pentaspline PFA catheter. Procedure and left atrial dwell times, with a 20-min waiting period, were 71.9 ± 17.6 and 41.0 ± 13.3 min, respectively. Fluoroscopy time was 11.5 ± 7.4 min. Notably, monitoring compliance was high, with 88.4 and 90.3% with weekly events and 72-h Holter monitors, respectively. Freedom from the composite primary effectiveness endpoint was 66.6%, and 41 patients had atrial tachyarrhythmia recurrence, mostly recurrent atrial fibrillation (31 patients). The composite safety endpoint occurred in two patients (1.1%), one tamponade and one transient ischaemic attack. There was no coronary spasm, PV stenosis, or AE fistula. There were four cases of transient phrenic nerve palsy, but all resolved during the index procedure. CONCLUSION: In this prospective, non-randomized, multicentre study, PVI using a pentaspline PFA catheter was effective in treating PAF patients despite rigourous endpoint definitions and high monitoring compliance and demonstrated favourable safety. REGISTRATION: Clinical Trials.gov Identifier: NCT05072964 (sponsor: Boston Scientific Corporation).


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Fístula , Venas Pulmonares , Femenino , Humanos , Masculino , Antiarrítmicos , Fibrilación Atrial/cirugía , Ablación por Catéter/métodos , Constricción Patológica/cirugía , Fístula/cirugía , Estudios Prospectivos , Venas Pulmonares/cirugía , Recurrencia , Taquicardia/cirugía , Resultado del Tratamiento , Persona de Mediana Edad , Anciano
12.
J Cardiovasc Electrophysiol ; 35(1): 94-96, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38031813
13.
Ir J Med Sci ; 193(1): 341-343, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37340226

RESUMEN

BACKGROUND: Plain film abdomens (PFA) are frequently used in the emergency department to help guide the management of patients presenting with abdominal symptoms. A plain film abdomen contributes minimally to clinical scenarios due to low sensitivity and specificity. Is a PFA useful in the emergency setting or does it serve to further complicate decision making? AIM: We hypothesise that PFAs in the emergency department are over utilised to falsely reassure clinicians and patients alike. METHODS: A search of the National Integrated Medical Imaging System (NIMIS) database in an Irish tertiary referral hospital was conducted. All plain film abdominal radiographs requested by the emergency department between 01/01/2022 and 31/08/2022 were identified. Requests where there was suspicion of foreign body were excluded. A retrospective search of the NIMIS database identified subjects who underwent subsequent imaging. RESULTS: A total of 619 abdominal films were deemed suitable for inclusion. These comprised of 338 male and 282 female subjects. Subjects had an average age of 64 years. Fifty-seven per cent of PFAs detected no abnormality. Forty-two per cent of subjects had subsequent imaging. The plain film findings correlated with further imaging in only 15% of cases. One case of ruptured aortic aneurysm and 11 perforations were detected on computerised tomography, none of these cases were evident on abdominal X-ray. CONCLUSION: Plain film abdomen requests are over utilised in the emergency department. PFAs are not sensitive for detecting acute pathology and should not be used to decide if a patient requires further imaging or a full clinical assessment.


Asunto(s)
Abdomen , Fluorocarburos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Radiografía Abdominal , Tomografía Computarizada por Rayos X , Servicio de Urgencia en Hospital
14.
Proc Natl Acad Sci U S A ; 120(51): e2308088120, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38091295

RESUMEN

Aldehydes fixation was accidentally discovered in the early 20th century and soon became a widely adopted practice in the histological field, due to an excellent staining enhancement in tissues imaging. However, the fixation process itself entails cell proteins denaturation and crosslinking. The possible presence of artifacts, that depends on the specific system under observation, must therefore be considered to avoid data misinterpretation. This contribution takes advantage of scanning electron assisted-dielectric microscopy (SE-ADM) and Raman 2D imaging to reveal the possible presence and the nature of artifacts in unstained, and paraformldehyde, PFA, fixed MNT-1 cells. The high resolution of the innovative SE-ADM technique allowed the identification of globular protein clusters in the cell cytoplasm, formed after protein denaturation and crosslinking. Concurrently, SE-ADM images showed a preferential melanosome adsorption on the cluster's outer surface. The micron-sized aggregates were discernible in Raman 2D images, as the melanosomes signal, extracted through 2D principal component analysis, unequivocally mapped their location and distribution within the cells, appearing randomly distributed in the cytoplasm. Protein clusters were not observed in living MNT-1 cells. In this case, mature melanosomes accumulate preferentially at the cell periphery and are more closely packed than in fixed cells. Our results show that, although PFA does not affect the melanin structure, it disrupts melanosome distribution within the cells. Proteins secondary structure, conversely, is partially lost, as shown by the Raman signals related to α-helix, ß-sheets, and specific amino acids that significantly decrease after the PFA treatment.


Asunto(s)
Melaninas , Melanosomas , Microscopía Electrónica de Rastreo , Melanosomas/metabolismo , Melaninas/metabolismo
15.
Nanomaterials (Basel) ; 13(24)2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38133021

RESUMEN

Photocatalytic coatings can degrade volatile organic compounds into non-toxic products, which has drawn the attention of scholars around the world. However, the pollution of dust on the coating adversely affects the photocatalytic efficiency and service life of the coating. Here, a series of TiO2-polyfluoroalkoxy (PFA) coatings with different contents of PFA were fabricated by suspension plasma spraying technology. The results demonstrate that the hybrid coatings contain a large number of circular and ellipsoidal nanoparticles and a porous micron-nano structure due to the inclusion of PFA. According to the optimized thermal spraying process parameters, TiO2 nanoparticles were partially melted to retain most of the anatase phases, whereas PFA did not undergo significant carbonization. As compared to the TiO2 coating, the static contact angle of the composite coating doped with 25 wt.% PFA increased from 28.2° to 134.1°. In addition, PFA strongly adsorbs methylene blue, resulting in a greater involvement of methylene blue molecules in the catalyst, where the catalytic rate of hybrid coatings is up to 95%. The presented nanocomposite coatings possess excellent photocatalytic and self-cleaning properties and are expected to find wider practical applications in the field of photocatalysis.

16.
Cureus ; 15(10): e47832, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37899902

RESUMEN

INTRODUCTION: Thrombophilic genetic polymorphisms of the platelet glycoproteins Ia (GpIa) and IIIa (GpIIIa) have been associated with an increased risk of recurrent miscarriages. The aim of this study was to investigate the association of genetic polymorphisms GpIa-C807T and GpIIIa-T1565C-PlA1/PlA2 with platelet function in women with unexplained spontaneous recurrent miscarriages. METHODS: This cross-sectional study comprised 196 unrelated nulliparous Greek women with a history of unexplained recurrent miscarriages. Patients were genotyped for the presence of the GpIa-C807T (rs1126643) and GpIIIa-T1565C-PlA1/PlA2 (rs5918) genetic polymorphisms by pyrosequencing, and the collagen/epinephrine closure time (COL/EPI CT) of the subjects was assessed using the platelet function analyzer (PFA)-100. RESULTS:  In the total population of women with recurrent miscarriages, the COL/EPI CT ranged from 70 to 160 seconds (median: 122 seconds, interquartile range (IQR): 102.3-138 seconds). In comparison with the double homozygotes CC/PlA1PlA1 that had the most prolonged CT (mean: 131.9 ± 17.5 seconds), the COL/EPI CT was statistically significantly shorter for the GpIa-807T single carriers (mean: 120.3 ± 20.9 seconds) (p=0.011) (absolute difference: 11.6 seconds, 95% confidence interval (CI): 21.2 to -2.0 seconds; relative difference: -9%, 95% CI: -16% to -2%), and the GpIIIa-PlA2 single carriers also displayed a trend for shorter COL/EPI CT (mean: 121.3 ± 23.7 seconds) (p=0.141) (absolute difference: -10.6 seconds, relative difference: -8%), whereas the combined carriers of the GpIa-807T and the GpIIIa-PlA2 alleles exhibited the shortest COL/EPI CT (mean: 104.1 ± 19.7 seconds) (absolute difference: -27.7 seconds, 95% CI: -39.1 to -16.3 seconds; relative difference: -21%, 95% CI: -30% to -12%) (p<0.001). In comparing genotype frequencies in the lower half with those in the upper half of the COL/EPI CT range, the GpIa-807T and the GpIIIa-PlA2 single carriers were associated with higher odds of COL/EPI CT < 122 seconds (odds ratio (OR)=3.4, 95% CI: 1.5 to 7.5, p=0.002, and OR=2.6, 95% CI: 1.0 to 7.2, p=0.053, respectively). The association was strongest for the combined carriers with OR of 15.0 (95% CI: 5.2 to 43.2, p<0.001) for COL/EPI CT below the median and OR of 35.5 (95% CI: 4.4 to 284.5, p<0.001) for COL/EPI CT < 100 seconds. CONCLUSION: The GpIa-C807T and GpIIIa-PlA1/PlA2 polymorphisms and more pronouncedly the combined carriers of the risk variants are associated with enhanced platelet reactivity expressed via shorter COL/EPI CT. These findings provide further evidence for the role of platelet-associated genetic thrombophilia in the pathogenesis of recurrent miscarriages and promote the analysis of platelet function as a diagnostic tool in the evaluation of this disorder.

17.
eNeuro ; 10(9)2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37709524

RESUMEN

Chemical fixation using paraformaldehyde (PFA) is a standard step for preserving cells and tissues for subsequent microscopic analyses such as immunofluorescence or electron microscopy (EM). However, chemical fixation may introduce physical alterations in the spatial arrangement of cellular proteins, organelles, and membranes. With the increasing use of super-resolution microscopy to visualize cellular structures with nanometric precision, assessing potential artifacts, and knowing how to avoid them, takes on special urgency. We addressed this issue by taking advantage of live-cell super-resolution microscopy that makes it possible to directly observe the acute effects of PFA on organotypic hippocampal brain slices, allowing us to compare tissue integrity in a "before-and-after" experiment. We applied super-resolution shadow imaging (SUSHI) to assess the structure of the extracellular space (ECS) and regular super-resolution microscopy of fluorescently labeled neurons and astrocytes to quantify key neuroanatomical parameters. While the ECS volume fraction (VF) and microanatomic organization of astrocytes remained largely unaffected by the PFA treatment, we detected subtle changes in dendritic spine morphology and observed substantial damage to cell membranes. Our experiments show that PFA application via immersion does not cause a noticeable shrinkage of the ECS in hippocampal brain slices maintained in culture, unlike the situation in transcardially perfused animals in vivo where the ECS typically becomes nearly depleted. Our study outlines an experimental strategy to evaluate the quality and pitfalls of various fixation protocols for the molecular and morphologic preservation of cells and tissues.


Asunto(s)
Artefactos , Microscopía , Animales , Ratones , Astrocitos , Encéfalo , Hipocampo
18.
Anal Bioanal Chem ; 415(26): 6389-6398, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37640826

RESUMEN

Infrared matrix-assisted laser desorption electrospray ionization mass spectrometry imaging (IR-MALDESI) conventionally utilizes fresh-frozen biological tissues with an ice matrix to improve the detection of analytes. Sucrose-embedding with paraformaldehyde fixation has demonstrated feasibility as an alternative matrix for analysis by IR-MALDESI by preserving tissue features and enhancing ionization of lipids. However, investigating multi-organ systems provides broader context for a biological study and can elucidate more information about a disease state as opposed to a single organ. Danio rerio, or zebrafish, are model organisms for various disease states and can be imaged as a multi-organ sample to analyze morphological and metabolomic preservation as a result of sample preparation. Herein, whole-body zebrafish were imaged to compare sucrose-embedding with paraformaldehyde fixation against conventional fresh-frozen sample preparation. Serial sections were analyzed with and without an ice matrix to evaluate if sucrose functions as an alternative energy-absorbing matrix for IR-MALDESI applications across whole-body tissues. The resulting four conditions were compared in terms of total putative lipid annotations and category diversity, coverage across the entire m/z range, and ion abundance. Ultimately, sucrose-embedded zebrafish had an increase in putative lipid annotations for the combination of putative annotations with and without the application of an ice matrix relative to fresh-frozen tissues which require the application of an ice matrix. Upon the use of an ice matrix, a greater number of high mass putative lipid annotations (e.g., glycerophospholipids, glycerolipids, and sphingolipids) were identified. Conversely, without an ice matrix, sucrose-embedded sections elucidated more putative annotations in lower molecular weight lipids, including fatty acyls and sterol lipids. Similar to the mouse brain model, sucrose-embedding increased putative lipid annotation and abundance for whole-body zebrafish.

19.
Clin Appl Thromb Hemost ; 29: 10760296231187627, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37563887

RESUMEN

The value of platelet function test in timing of cardiac surgery remains uncertain. Researches on correlation between Platelet Function Analyzer 200 (PFA-200) and bleeding after elective cardiac surgery are still inadequate. The objective of this study was to investigate the predictive value of PFA-200 in blood transfusion after cardiac surgery. A total of 71 patients on aspirin and P2Y12 receptor inhibitors undergoing cardiac surgery in Fuwai Hospital were enrolled. Platelet function after discontinuing of antiplatelet drugs was assessed by PFA-200 using closure time (CT). PFA-200 results before surgery were included in the statistics. The primary endpoint was postoperative blood transfusion. Seventeen patients (21.9%) received blood transfusion after cardiac surgery. The preoperative PFA-200 CT value in the transfused group was significantly higher than that in the non-transfused group (147.24 ± 85.54 s vs 98.06 ± 61.59 s, P = .011). Using 106 seconds as the dividing point, the incidence of blood transfusion in the elevated PFA-200 (CT > 106 s) group was significantly higher than those in normal PFA-200 (CT ≤ 106 s) group (10/24 patients, 41.9% vs 7/47 patients, 14.7%, P = .012). Multivariate logistic regression analysis showed that PFA-200 CT value > 106 s was an independent predictor of postoperative blood transfusion (OR: 4.05, 95%CI: 1.19-13.86, P = .026). The platelet function test PFA-200 had a predictive value for postoperative blood transfusion in elective cardiac surgery and had a promising prospect in the timing of cardiac surgery.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Inhibidores de Agregación Plaquetaria , Humanos , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Aspirina/uso terapéutico , Aspirina/farmacología , Plaquetas , Pruebas de Función Plaquetaria/métodos , Transfusión Sanguínea
20.
Materials (Basel) ; 16(15)2023 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-37569995

RESUMEN

Semiconductor cleaning system ultra-clean flow control pumps are critical equipment in the semiconductor industry. Among them, the perfluoroalkoxy alkane (PFA) spring is a pivotal component to control the pump, and its dynamic performance is crucial to ensure the efficient operation of the system. However, the dynamic performance of the spring is often affected by the operating frequency. This paper studied the effect of different working frequencies on the dynamic property of the spring through compression-cycle experiments under uniaxial sinusoidal excitation. The force-displacement curves under different compression frequencies were fitted to obtain the dynamic stiffness of the PFA spring under different cyclic loading frequencies. The variation in the spring's hysteresis coefficient was evaluated using the hysteresis curves of different cyclic loading conditions. After 2 million compression experiments, the changes in dynamic stiffness, hysteresis coefficient, and spring height were investigated. The obtained results revealed that, as the frequency increases, the dynamic stiffness of the spring increases. The hysteresis coefficient of the PFA spring is the largest at 10 Hz and the smallest at 6 Hz. Upon conducting 2 million compression tests, it was discovered that the dynamic stiffness experiences the greatest attenuation rate of 4.19% at a frequency of 8 Hz, whereas the hysteresis coefficient undergoes the largest attenuation of 42.1% at a frequency of 6 Hz. The results will help to improve the design and application level of PFA springs.

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