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1.
Cult Med Psychiatry ; 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38864972

RESUMEN

Loneliness among young people has been increasing in recent years and is considered a major public health problem. This article delves into the sociocultural dynamics that favour the experiences of loneliness. For this purpose, 40 students between 19 and 24 years of age were interviewed using the photo elicitation interview (PEI) strategy. The results show a gradual normalization of the experience of loneliness and an effort to become accustomed to it. Virtual relationships and isolation linked to the COVID-19 pandemic are considered the two factors that have most enabled a climate prone to loneliness. Young people identify a few elements that feed social loneliness, such as an understanding of instrumental relationships, a scarcity of intimate relationships, a demand for hyperconnectivity, a fantasy of independence and a culture of positivity that hinders the establishment of quality social ties. Faced with hostile relational conditions, youth are sent into a cycle of loneliness. The greater the distrust of the environment is, the greater the defensive reactions and social distancing, and the greater the search for nearby spaces of refuge, security and shelter. Social withdrawal makes in-person relationships difficult and strengthens the need to isolate and become accustomed to loneliness.

2.
bioRxiv ; 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38746443

RESUMEN

Physical exercise represents a primary defense against age-related cognitive decline and neurodegenerative disorders like Alzheimer's disease (AD). To impartially investigate the underlying mechanisms, we conducted single-nucleus transcriptomic and chromatin accessibility analyses (snRNA-seq and ATAC-seq) on the hippocampus of mice carrying AD-linked NL-G-F mutations in the amyloid precursor protein gene (APPNL-G-F) following prolonged voluntary wheel-running exercise. Our study reveals that exercise mitigates amyloid-induced changes in both transcriptomic expression and chromatin accessibility through cell type-specific transcriptional regulatory networks. These networks converge on the activation of growth factor signaling pathways, particularly the epidermal growth factor receptor (EGFR) and insulin signaling, correlating with an increased proportion of immature dentate granule cells and oligodendrocytes. Notably, the beneficial effects of exercise on neurocognitive functions can be blocked by pharmacological inhibition of EGFR and the downstream phosphoinositide 3-kinases (PI3K). Furthermore, exercise leads to elevated levels of heparin-binding EGF (HB-EGF) in the blood, and intranasal administration of HB-EGF enhances memory function in sedentary APPNL-G-F mice. These findings offer a panoramic delineation of cell type-specific hippocampal transcriptional networks activated by exercise and suggest EGF-related growth factor signaling as a druggable contributor to exercise-induced memory enhancement, thereby suggesting therapeutic avenues for combatting AD-related cognitive decline.

3.
J Am Chem Soc ; 146(21): 14856-14863, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38717994

RESUMEN

Uranyl fluoride (UO2F2) particles (<20 µm) were subjected to first-of-its-kind analysis via simultaneous laser-induced breakdown spectroscopy (LIBS) and laser ablation multi-collector inductively coupled plasma-mass spectrometry (LA-MC-ICP-MS). Briefly, a nanosecond pulsed high-energy laser was focused onto the sample (particle) surface. In a single laser pulse, the UO2F2 particle was excited/ionized within the microplasma volume, and the emission of light was collected via fiber optics such that emission spectroscopy could be employed for the detection of uranium (U) and fluorine (F). The ablated particle was simultaneously transported into the MC-ICP-MS for high precision isotopic (i.e., 234U, 235U, and 238U) analysis. This method, LIBS/LA-MC-ICP-MS was optimized and employed to rapidly measure 80+ UO2F2 particles, which were subjected to different calcination processes, which results in varying degrees of F loss from the individual particles. In measuring the particles, the average F/U ratios for the populations treated at 100 and 500 °C were 2.78 ± 1.28 and 1.01 ± 0.50, respectively, confirming loss of F through the calcination process. The average 235U/238U on the particle populations for the 100 and 500 °C were 0.007262 (22) and 0.007231 (23), which was determined to be <0.2% from the expected value. The 234U/238U ratios on the same particles were 0.000053 (11) and 0.000050 (10) for the 100 and 500 °C, respectively, <10% from the expected value. Notably, each population was analyzed in under 5 min, demonstrating the truly rapid analysis technique presented here.

4.
Am Surg ; : 31348241248813, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38716696

RESUMEN

Background: In previous studies, breast cancer patients with positive sentinel lymph node(s) (SLN) after neoadjuvant chemotherapy (NAC) frequently had additional nonSLN involvement. Per guidelines, residual SLN disease warrants completion axillary lymph node dissection (cALND), which has increased morbidity. Given recent improvements in NAC, we hypothesized that nonSLN positivity may be lower than previously reported for certain subgroups.Methods: We retrospectively reviewed breast cancer patients who received NAC and had positive lymph nodes on SLN biopsy or targeted axillary dissection and underwent cALND at one institution in 1/2018-8/2023. Associations between nonSLN positivity and clinicopathologic factors were assessed with Fisher's exact test and multivariable logistic regression.Results: There were 122 female patients. Median age was 48 years. Initially, 15 patients (12.3%) were cN0 and 107 patients (87.7%) were cN1. Largest SLN deposit was macrometastasis in 96 patients (78.7%), micrometastasis in 23 patients (18.9%), and isolated tumor cells in 3 patients (2.5%). Overall, 53 patients (43.4%) had nonSLN involvement. NonSLN positivity was higher in patients with cN1, ER+ HER2-, ypT2-3, SLN macrometastasis, and multiple positive SLN. On multivariable analysis, cN1 and ER+ HER2- remained associated with nonSLN positivity.Discussion: Among patients with positive SLN after NAC, clinically node positive and ER+ HER2- patients were more likely to have nonSLN involvement. Our findings support guidelines to consider omitting cALND in clinically node negative patients. With improving NAC, optimal axillary sampling, and radiation, omitting cALND may be safe in some clinically node positive triple negative or HER2+ patients with low volume residual disease, but further research is needed.

5.
Anal Methods ; 16(20): 3192-3201, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38639200

RESUMEN

This work describes an analytical procedure, single particle-inductively coupled plasma-time-of-flight-mass spectrometry (SP-ICP-TOF-MS), that was developed to determine the platinum binding efficiency of protein-coated magnetic microparticles. SP-ICP-TOF-MS is advantageous due to its ability to quasi-simultaneously detect all nuclides (7Li-242Pu), allowing for both platinum and iron (composition of magnetic microparticles) to be measured concurrently. This method subsequently allows for the differentiation between bound and unbound platinum. The 1 µm magnetic microparticles were fully characterized for their iron concentration, particle concentration, and trace element composition by bulk digestion-ICP-MS and SP-ICP-TOF-MS. The results of both approaches agreed with the certificate values. Using the single particle methodology the platinum loading was quantified to be to 0.18 ± 0.02 fg per particle and 0.32 ± 0.02 fg per particle, for the streptavidin-coated and azurin-coated microparticles, respectively. Both streptavidin-coated and the azurin-coated microparticles had a particle-platinum association of >65%. Platinum bound samples were also analyzed via bulk digestion-based ICP-MS. The bulk ICP-MS results overestimated platinum loading due to free platinum in the samples. This highlights the importance of single particle analysis for a closer inspection of platinum binding performance. The SP-ICP-TOF-MS approach offers advantages over typical bulk digestion methods by eliminating laborious sample preparation, enabling differentiation between bound/unbound platinum in a solution, and quantification of platinum on a particle-by-particle basis. The procedure presented here enables quantification of metal content per particle, which could be broadly implemented for other single particle applications.


Asunto(s)
Espectrometría de Masas , Platino (Metal) , Platino (Metal)/química , Espectrometría de Masas/métodos , Microesferas , Hierro/química , Hierro/análisis , Estreptavidina/química , Tamaño de la Partícula , Nanopartículas de Magnetita/química
6.
Health Equity ; 8(1): 206-225, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38559844

RESUMEN

Background: Food insecurity is a major public health concern in the United States, particularly for pregnant and postpartum individuals. In 2020, ∼13.8 million (10.5%) U.S. households experienced food insecurity. However, the association between food security and pregnancy outcomes in the United States is poorly understood. Purpose: The purpose of this review was to critically appraise the state of the evidence related to food insecurity as a determinant of health within the context of pregnancy in the United States. We also explored the relationship between food insecurity and pregnancy outcomes. Methods: PubMed, CINAHL, Web of Science, and Food and Nutrition Science databases were used. The inclusion criteria were peer-reviewed studies about food (in)security, position articles from professional organizations, and policy articles about pregnancy outcomes and breastfeeding practices. Studies conducted outside of the United States and those without an adequate definition of food (in)security were excluded. Neonatal health outcomes were also excluded. Included articles were critically appraised with the STROBE and Critical Appraisal Skills Program checklists. Results: Nineteen studies met the inclusion criteria. Inconsistencies exist in defining and measuring household food (in)security. Pregnant and postpartum people experienced several adverse physiological and psychological outcomes that impact pregnancy compared with those who do not. Intersections between neighborhood conditions and other economic hardships were identified. Findings regarding the impact of food insecurity on breastfeeding behaviors were mixed, but generally food insecurity was not associated with poor breastfeeding outcomes in adjusted models. Conclusion: Inconsistencies in definitions and measures of food security limit definitive conclusions. There is a need for standardizing definitions and measures of food insecurity, as well as a heightened awareness and policy change to alleviate experiences of food insecurity.

7.
Vox Sang ; 119(6): 619-623, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38451394

RESUMEN

BACKGROUND AND OBJECTIVES: Until 25 July 2022, Australians who had spent more than 6 months in the United Kingdom or territories between 1980 and 1996 were deferred from blood donation due to the risk of variant Creutzfeldt-Jakob disease. Removal of this geography-based donor deferral on RhD-negative blood availability has not been reported. MATERIALS AND METHODS: All donors who donated at least once from 25 July 2022 to 25 July 2023 were included. UK donor status, first-time donor and ABO RhD data were extracted from the National Blood Management System. RESULTS: Data from 566,447 blood donors with a valid ABO RhD result were analysed. Of these, 34,560 were new or returning lapsed donors following removal of the UK donor deferral. The median age [range] in years for all donors was 43 [75] with UK donors being older 53 [70]. There was a higher prevalence of RhD-negative status in UK donors (20.2%) compared with first-time blood donors (15.7%). CONCLUSION: UK donors were generally older, female and more likely to be RhD-negative. Although UK donors provided a boost to RhD-negative blood collections, the overall prevalence of ABO RhD blood groups in the total Australian blood donor panel remained similar to previous estimates.


Asunto(s)
Sistema del Grupo Sanguíneo ABO , Donantes de Sangre , Síndrome de Creutzfeldt-Jakob , Sistema del Grupo Sanguíneo Rh-Hr , Humanos , Femenino , Australia/epidemiología , Síndrome de Creutzfeldt-Jakob/sangre , Síndrome de Creutzfeldt-Jakob/epidemiología , Masculino , Persona de Mediana Edad , Adulto , Anciano , Reino Unido/epidemiología , Selección de Donante
9.
Ann Biomed Eng ; 52(6): 1625-1637, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38409434

RESUMEN

Binding kinetics play an important role in cancer diagnosis and therapeutics. However, current methods of quantifying binding kinetics fail to consider the three-dimensional environment that drugs and imaging agents experience in biological tissue. In response, a methodology to assay agent binding and dissociation in 3-D tissue culture was developed using paired-agent molecular imaging principles. To test the methodology, the uptakes of ABY-029 (an IRDye 800CW-labeled epidermal growth factor receptor (EGFR)-targeted antibody mimetic) and IRDye-700DX carboxylate in 3-D spheroids were measured in four different human cancer cell lines throughout staining and rinsing. A compartment model (optimized for the application) was then fit to the kinetic curves of both imaging agents to estimate binding and dissociation rate constants of the EGFR-targeted ABY-029 agent. A statistically significant correlation was observed between apparent association rate constant (k3) and the receptor concentration experimentally and in simulations (r = 0.99, p < 0.05). A statistically significant difference was found between effective k3 (apparent rate constant of ABY-029 binding to EGFR) values for cell lines with varying levels of EGFR expression (p < 0.05), with no significant difference found between cell lines and controls for other fit parameters. Additionally, a similar binding affinity profile compared to a gold standard method was determined by this model. This low-cost methodology to quantify imaging agent or drug binding affinity in clinically relevant 3-D tumor spheroid models can be used to guide timing of imaging in molecular guided surgery and could have implications in drug development.


Asunto(s)
Receptores ErbB , Esferoides Celulares , Humanos , Esferoides Celulares/metabolismo , Receptores ErbB/metabolismo , Línea Celular Tumoral , Neoplasias/metabolismo , Neoplasias/diagnóstico por imagen , Neoplasias/patología , Técnicas de Cultivo Tridimensional de Células
10.
Adv Mater ; 36(23): e2312326, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38389502

RESUMEN

Clinical treatment of cancer commonly incorporates X-ray radiation therapy (XRT), and developing spatially precise radiation-activatable drug delivery strategies may improve XRT efficacy while limiting off-target toxicities associated with systemically administered drugs. Nevertheless, achieving this has been challenging thus far because strategies typically rely on radical species with short lifespans, and the inherent nature of hypoxic and acidic tumor microenvironments may encourage spatially heterogeneous effects. It is hypothesized that the challenge could be bypassed by using scintillating nanoparticles that emit light upon X-ray absorption, locally forming therapeutic drug depots in tumor tissues. Thus a nanoparticle platform (Scintillating nanoparticle Drug Depot; SciDD) that enables the local release of cytotoxic payloads only after activation by XRT is developed, thereby limiting off-target toxicity. As a proof-of-principle, SciDD is used to deliver a microtubule-destabilizing payload MMAE (monomethyl auristatin E). With as little as a 2 Gy local irradiation to tumors, MMAE payloads are released effectively to kill tumor cells. XRT-mediated drug release is demonstrated in multiple mouse cancer models and showed efficacy over XRT alone (p < 0.0001). This work shows that SciDD can act as a local drug depot with spatiotemporally controlled release of cancer therapeutics.


Asunto(s)
Nanopartículas , Animales , Nanopartículas/química , Ratones , Humanos , Línea Celular Tumoral , Liberación de Fármacos , Preparaciones de Acción Retardada/química , Oligopéptidos/química , Antineoplásicos/química , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Portadores de Fármacos/química
11.
Biomedicines ; 12(2)2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38398062

RESUMEN

Acidosis is an important immunosuppressive mechanism that leads to tumor growth. Therefore, we investigated the neutralization of tumor acidity to improve immunotherapy response. L-DOS47, a new targeted urease immunoconjugate designed to neutralize tumor acidity, has been well tolerated in phase I/IIa trials. L-DOS47 binds to CEACAM6, a cell-surface protein that is highly expressed in gastrointestinal cancers, allowing urease to cleave endogenous urea into two NH4+ and one CO2, thereby raising local pH. To test the synergetic effect of neutralizing tumor acidity with immunotherapy, we developed a pancreatic orthotopic murine tumor model (KPC961) expressing human CEACAM6. Using chemical exchange saturation transfer-magnetic resonance imaging (CEST-MRI) to measure the tumor extracellular pH (pHe), we confirmed that L-DOS47 raises the tumor pHe from 4 h to 96 h post injection in acidic tumors (average increase of 0.13 units). Additional studies showed that combining L-DOS47 with anti-PD1 significantly increases the efficacy of the anti-PD1 monotherapy, reducing tumor growth for up to 4 weeks.

12.
Analyst ; 149(8): 2244-2251, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38415746

RESUMEN

A microextraction liquid sampling system coupled to a quadrupole inductively coupled plasma-mass spectrometer (ICP-MS) was utilized to spatially discern uranium particles, isotopically, on a cellulose-based swipe material (i.e., J-type swipe). These types of swipes are often used by the International Atomic Energy Agency (IAEA) as part of their environmental sampling program. A grid was created such that extraction locations covered the center circle (n = 34 without overlapping). Uranium (U) particulates (<20 µm) of varying U isotopic abundance and chemical form (i.e., uranyl fluoride and uranyl nitrate hexahydrate) were mechanically placed on the swipes in random locations and detected via the microextraction-ICP-MS methodology. Heat maps were subsequently generated to show the placement of the particulate with their respective intensity and isotopic determination. This detection of the uranium particulates, via isotopic determination, agreed with reference values for these materials. Additionally, depleted (235U/238U = 0.002) uranium particulates were placed directly within a clay matrix, on the swipe surface, and subjected to analysis by microextraction-ICP-MS. The mapping of the swipe demonstrated, for the first time, the employment of the microextraction-ICP-MS method for extracting sample from a complex matrix, and correctly identifying the uranium isotopic composition. This example ultimately demonstrates the utility of the methodology for detecting particles of interest in complex matrices.

13.
Front Bioeng Biotechnol ; 12: 1337879, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38303911

RESUMEN

The combination of a sensitive and specific magnetoresistive sensing device with an easy DNA extraction method and a rapid isothermal amplification is presented here targeting the on-site detection of Globodera pallida, a potato endoparasitic nematode. FTA-cards were used for DNA extraction, LAMP was the method developed for DNA amplification and a nanoparticle functionalized magnetic-biosensor was used for the detection. The combinatorial effect of these three emerging technologies has the capacity to detect G. pallida with a detection limit of one juvenile, even when mixed with other related species. This combined system is far more interesting than what a single technology can provide. Magnetic biosensors can be combined with any DNA extraction protocol and LAMP forming a new solution to target G. pallida. The probe designed in this study consistently distinguished G. pallida (∆Vac binding/Vac sensor above 1%) from other cyst nematodes (∆Vac binding/Vac sensor below 1%). It was confirmed that DNA either extracted with FTA-cards or Lab extraction Kit was of enough quantity and quality to detect G. pallida whenever present (alone or in mixed samples), ensuring probe specificity and sensitivity. This work provides insights for a new strategy to construct advanced devices for pathogens in-field diagnostics. LAMP runs separately but can be easily integrated into a single device.

14.
J Med Imaging Radiat Sci ; 55(1): 91-96, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38216344

RESUMEN

OBJECTIVE: To determine the diagnostic accuracy of Bone Scan at different PSA levels for detecting skeletal metastases in men with biochemical recurrence of prostate cancer. METHODS: We conducted a retrospective review of the statewide RIS-PACS to identify 251 men with biochemical recurrence who underwent both a Bone Scan and Ga68 PSMA PET/CT (within 2 months of each other) between September 2019 and December 2022 at a single institution. The Ga68 PSMA PET/CT report was considered to be the reference standard. RESULTS: The median age was 72 years (IQR 67-76) with a median PSA level of 1 ng/ml (IQR 0.25-2.8). Using Ga68 PSMA PET/CT as the reference standard, 68/251 patients (25%) were positive for osseus metastases. Overall sensitivity and specificity of Bone Scan was 51% (95% CI 40-64%) and 99% (95% CI 98-100%) respectively. Using PSA banding, a PSA threshold of 20 ng/ml provided the greatest discriminatory benefit with sensitivity of the Bone Scan below the threshold being 46% (95% CI 33-59%) and above the threshold being 89% (95% CI 68-100%). Specificity remained consistently high both below and above this threshold. CONCLUSION: Bone Scan provides greater diagnostic accuracy for detecting skeletal metastases in biochemical recurrence when the PSA level is above 20 ng/ml. This knowledge is valuable in optimising imaging algorithms in biochemical recurrence, particularly in regions where PSMA PET/CT is less readily available or affordable.


Asunto(s)
Antígeno Prostático Específico , Neoplasias de la Próstata , Masculino , Humanos , Anciano , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radioisótopos de Galio , Isótopos de Galio , Oligopéptidos , Ácido Edético , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología
15.
Exp Dermatol ; 33(1): e14949, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37864429

RESUMEN

Intraoperative margin analysis is crucial for the successful removal of cutaneous squamous cell carcinomas (cSCC). Artificial intelligence technologies (AI) have previously demonstrated potential for facilitating rapid and complete tumour removal using intraoperative margin assessment for basal cell carcinoma. However, the varied morphologies of cSCC present challenges for AI margin assessment. The aim of this study was to develop and evaluate the accuracy of an AI algorithm for real-time histologic margin analysis of cSCC. To do this, a retrospective cohort study was conducted using frozen cSCC section slides. These slides were scanned and annotated, delineating benign tissue structures, inflammation and tumour to develop an AI algorithm for real-time margin analysis. A convolutional neural network workflow was used to extract histomorphological features predictive of cSCC. This algorithm demonstrated proof of concept for identifying cSCC with high accuracy, highlighting the potential for integration of AI into the surgical workflow. Incorporation of AI algorithms may improve efficiency and completeness of real-time margin assessment for cSCC removal, particularly in cases of moderately and poorly differentiated tumours/neoplasms. Further algorithmic improvement incorporating surrounding tissue context is necessary to remain sensitive to the unique epidermal landscape of well-differentiated tumours, and to map tumours to their original anatomical position/orientation.


Asunto(s)
Carcinoma Basocelular , Carcinoma de Células Escamosas , Aprendizaje Profundo , Neoplasias Cutáneas , Humanos , Carcinoma de Células Escamosas/patología , Cirugía de Mohs , Neoplasias Cutáneas/patología , Estudios Retrospectivos , Secciones por Congelación , Inteligencia Artificial , Carcinoma Basocelular/patología
16.
Breast Cancer Res Treat ; 203(2): 281-289, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37847456

RESUMEN

PURPOSE: The International Ki67 Working Group (IKWG) has developed training for immunohistochemistry (IHC) scoring reproducibility and recommends cut points of ≤ 5% and ≥ 30% for prognosis in ER+, HER2-, stage I/II breast cancer. We examined scoring reproducibility following IKWG training and evaluated these cut points for selecting patients for further testing with the 21-gene Recurrence Score (RS) assay. METHODS: We included 307 women aged 50+ years with node-negative, ER+PR+HER2- breast cancer and with available RS results. Slides from the diagnostic biopsy were stained for Ki67 and scored using digital image analysis (IA). Two IHC pathologists underwent IKWG training and visually scored slides, blinded to each other and IA readings. Interobserver reproducibility was examined using intraclass correlation (ICC) and Kappa statistics. RESULTS: Depending on reader, 8.8-16.0% of our cohort had Ki67 ≤ 5% and 11.4-22.5% had scores ≥ 30%. The ICC for Ki67 scores by the two pathologists was 0.82 (95% CI 0.78-0.85); it was 0.79 (95% CI 0.74-0.83) for pathologist 1 and IA and 0.76 (95% CI 0.71-0.80) for pathologist 2 and IA. For Ki67 scores ≤ 5%, the percentages with RS < 26 were 92.6%, 91.8%, and 90.9% for pathologist 1, pathologist 2, and IA, respectively. For Ki67 scores ≥ 30%, the percentages with RS ≥ 26 were 41.5%, 51.4%, and 27.5%, respectively. CONCLUSION: The IKWG's Ki67 training resulted in moderate to strong reproducibility across readers but cut points had only moderate overlap with RS cut points, especially for Ki67 ≥ 30% and RS ≥ 26; thus, their clinical utility for a 21-gene assay testing pathway remains unclear.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Antígeno Ki-67/metabolismo , Reproducibilidad de los Resultados , Pronóstico , Inmunohistoquímica , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis
17.
Vox Sang ; 119(2): 94-101, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37641582

RESUMEN

Many blood establishments are expanding plasmapheresis collection capacity to achieve increasing plasma for fractionation volume targets, driven by immunoglobulin product demand. Some adverse events occur in both apheresis and whole blood collection, such as venepuncture-related trauma and vasovagal reactions. Others are specifically related to the apheresis procedure, such as citrate reactions, haemolysis, infiltration and air embolism. Whilst plasmapheresis procedures are generally well tolerated, theoretical longer term donor health considerations, such as the effects on donor plasma protein levels, bone mineral density, iron deficiency and malignancy also require consideration. An evidence-based framework that supports a safe and sustainable increase in the collection of plasma is essential. Our review demonstrates a lack of high-quality evidence on risks and outcomes specifically in plasmapheresis. Whilst conservative procedural controls and donor harm minimization policies will mitigate risk, high-quality evidence is needed to facilitate practice change that is safe and sustainable and maximizes the potential of individual donor differences.


Asunto(s)
Eliminación de Componentes Sanguíneos , Plasmaféresis , Humanos , Plasmaféresis/efectos adversos , Eliminación de Componentes Sanguíneos/efectos adversos , Donantes de Sangre , Flebotomía , Plasma
18.
Int J Mol Sci ; 24(22)2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-38003584

RESUMEN

Diabetics are more vulnerable to SARS-CoV-2 neurological manifestations. The molecular mechanisms of SARS-CoV-2-induced cerebrovascular dysfunction in diabetes are unclear. We hypothesize that SARS-CoV-2 exacerbates diabetes-induced cerebrovascular oxidative stress and inflammation via activation of the destructive arm of the renin-angiotensin-aldosterone system (RAAS) and Toll-like receptor (TLR) signaling. SARS-CoV-2 spike protein was injected in humanized ACE2 transgenic knock-in mice. Cognitive functions, cerebral blood flow, cerebrovascular architecture, RAAS, and TLR signaling were used to determine the effect of SARS-CoV-2 spike protein in diabetes. Studies were mirrored in vitro using human brain microvascular endothelial cells treated with high glucose-conditioned media to mimic diabetic conditions. Spike protein exacerbated diabetes-induced cerebrovascular oxidative stress, inflammation, and endothelial cell death resulting in an increase in vascular rarefaction and diminished cerebral blood flow. SARS-CoV-2 spike protein worsened cognitive dysfunction in diabetes compared to control mice. Spike protein enhanced the destructive RAAS arm at the expense of the RAAS protective arm. In parallel, spike protein significantly exacerbated TLR signaling in diabetes, aggravating inflammation and cellular apoptosis vicious circle. Our study illustrated that SAR-CoV-2 spike protein intensified RAAS and TLR signaling in diabetes, increasing cerebrovascular damage and cognitive dysfunction.


Asunto(s)
COVID-19 , Diabetes Mellitus , Humanos , Ratones , Animales , Sistema Renina-Angiotensina , Glicoproteína de la Espiga del Coronavirus/metabolismo , SARS-CoV-2/metabolismo , COVID-19/complicaciones , Células Endoteliales/metabolismo , Enzima Convertidora de Angiotensina 2/metabolismo , Inflamación , Receptores Toll-Like/metabolismo , Ratones Transgénicos
19.
Anthropol Med ; 30(4): 362-379, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37781888

RESUMEN

Previous research on the stigma associated with cutaneous leishmaniasis, a vector-transmitted parasitic disease, focuses on aesthetic appearance affectation as the leading cause of stigmatisation. However, Indigenous populations in the hinterland of Amazonian Ecuador trigger stigma expressions by recognising (muco)cutaneous leishmaniasis, primarily through atypical smell, followed by the odd voice sound, appearance and taste. This empirical way of recognising symptoms relies on embodied forms of identifying a disease, contrasting the Western supremacy of visuality and demanding to be understood via multi-sensorial anthropology. Through ethnographic research and data retrieved from eighty-three semistructured interviews and fifteen focus groups in seven Ecuadorian ethnic groups - including six Indigenous groups in the Amazon region - this paper analyses how the sensorium is a health thermometer. Findings reveal that differentiated cultural responses to a sense of peril, contagion and social (self)rejection, understood as stigma expressions, are linked to the holistic approach to health (or well-being) shared by Indigenous populations. In forest societies, well-being is explained through successful (non-)human relationships, and disease permeates through bodies that lack balanced relations.


Asunto(s)
Leishmaniasis Cutánea , Humanos , Ecuador , Antropología Médica , Estigma Social , Antropología Cultural
20.
Anal Chem ; 95(43): 15867-15874, 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37801814

RESUMEN

The microextraction sampling technique was integrated with triple quadrupole─inductively coupled plasma-mass spectrometry (TQ-ICP-MS) to directly sample and measure the isotopic compositions of uranium (U) and plutonium (Pu) from cotton swipes. Once extracted, the U/Pu were directed into the TQ-ICP-MS instrument for isotopic determination. Carbon dioxide (CO2) and helium (He) gases were delivered to a collision reaction cell within the ICP-MS system for ion separation. The CO2 reacts with the U+ forming UO+ which is ultimately separated from the Pu+ ions of interest in the third quadrupole. This study demonstrates direct liquid extraction of U/Pu from a solid surface and subsequent measurement by TQ-ICP-MS in <60 s. Flow rates were optimized (0.3 mL min-1 CO2 and 5 mL min-1 He) in the reaction cell of the ICP-MS system to maximize the Pu signal while minimizing U interferences (i.e., 238U+ tail and 238UH+) at m/z 239. Low levels of Pu (∼2 pg) were deposited on a cotton swipe along with U at concentrations ranging from 20 to 200 ng. The 240Pu/239Pu ratio was measured with <7% relative difference from the certified value at all U concentrations. Major and minor U isotope ratios were also measured with <4% relative difference. This highlights that the microextraction-TQ-ICP-MS method can extract a mixed U/Pu sample directly from a cotton swipe and measure both isotopic systems without chemical separation.

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