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1.
Eur Radiol ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38780764

RESUMEN

MRI has gained prominence in the diagnostic workup of prostate cancer (PCa) patients, with the Prostate Imaging Reporting and Data System (PI-RADS) being widely used for cancer detection. Beyond PI-RADS, other MRI-based scoring tools have emerged to address broader aspects within the PCa domain. However, the multitude of available MRI-based grading systems has led to inconsistencies in their application within clinical workflows. The Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) assesses the likelihood of clinically significant radiological changes of PCa during active surveillance, and the Prostate Imaging for Local Recurrence Reporting (PI-RR) scoring system evaluates the risk of local recurrence after whole-gland therapies with curative intent. Underlying any system is the requirement to assess image quality using the Prostate Imaging Quality Scoring System (PI-QUAL). This article offers practicing radiologists a comprehensive overview of currently available scoring systems with clinical evidence supporting their use for managing PCa patients to enhance consistency in interpretation and facilitate effective communication with referring clinicians. KEY POINTS: Assessing image quality is essential for all prostate MRI interpretations and the PI-QUAL score represents  the standardized tool for this purpose. Current urological clinical guidelines for prostate cancer diagnosis and localization recommend adhering to the PI-RADS recommendations. The PRECISE and PI-RR scoring systems can be used for assessing radiological changes of prostate cancer during active surveillance and the likelihood of local recurrence after radical treatments respectively.

2.
J Inherit Metab Dis ; 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38356271

RESUMEN

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most prevalent mitochondrial fatty acid ß-oxidation disorder. In this study, we assessed the variability of the lipid profile in MCADD by analysing plasma samples obtained from 25 children with metabolically controlled MCADD (following a normal diet with frequent feeding and under l-carnitine supplementation) and 21 paediatric control subjects (CT). Gas chromatography-mass spectrometry was employed for the analysis of esterified fatty acids, while high-resolution C18-liquid chromatography-mass spectrometry was used to analyse lipid species. We identified a total of 251 lipid species belonging to 15 distinct lipid classes. Principal component analysis revealed a clear distinction between the MCADD and CT groups. Univariate analysis demonstrated that 126 lipid species exhibited significant differences between the two groups. The lipid species that displayed the most pronounced variations included triacylglycerols and phosphatidylcholines containing saturated and monounsaturated fatty acids, specifically C14:0 and C16:0, which were found to be more abundant in MCADD. The observed changes in the plasma lipidome of children with non-decompensated MCADD suggest an underlying alteration in lipid metabolism. Therefore, longitudinal monitoring and further in-depth investigations are warranted to better understand whether such alterations are specific to MCADD children and their potential long-term impacts.

3.
Proc Natl Acad Sci U S A ; 118(22)2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-34031240

RESUMEN

Storytelling is a distinctive human characteristic that may have played a fundamental role in humans' ability to bond and navigate challenging social settings throughout our evolution. However, the potential impact of storytelling on regulating physiological and psychological functions has received little attention. We investigated whether listening to narratives from a storyteller can provide beneficial effects for children admitted to intensive care units. Biomarkers (oxytocin and cortisol), pain scores, and psycholinguistic associations were collected immediately before and after storytelling and an active control intervention (solving riddles that also involved social interaction but lacked the immersive narrative aspect). Compared with the control group, children in the storytelling group showed a marked increase in oxytocin combined with a decrease in cortisol in saliva after the 30-min intervention. They also reported less pain and used more positive lexical markers when describing their time in hospital. Our findings provide a psychophysiological basis for the short-term benefits of storytelling and suggest that a simple and inexpensive intervention may help alleviate the physical and psychological pain of hospitalized children on the day of the intervention.


Asunto(s)
Comunicación , Hidrocortisona/metabolismo , Oxitocina/metabolismo , Dolor/metabolismo , Saliva/metabolismo , Atención , Biomarcadores/metabolismo , Niño , Preescolar , Emociones , Femenino , Humanos , Masculino , Manejo del Dolor
4.
Arch Gynecol Obstet ; 309(6): 2315-2321, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38502190

RESUMEN

PURPOSE: Obesity`s prevalence is rising in women of reproductive age worldwide and has become the most common medical condition at this age group. Besides, its occurrence is also rising during pregnancy. This condition not only increases the risk of noncommunicable diseases on the mother, such as cardiovascular disease and diabetes, but also transfers this risk to the offspring. METHODS: This is a narrative review based on scientific and review articles on the matter. RESULTS: Obesity is associated with an increased risk of gestational diabetes mellitus, gestational hypertension and preeclampsia, venous thromboembolism, infection, and mental health problems. Furthermore, it has an impact on the progress of labor and induction matters. Regarding offspring outcomes, it is related to higher incidence of congenital anomalies, perinatal mortality, and the occurrence of large for gestational age newborns. Still, it has implications on cardiometabolic risk and neurodevelopment in offspring. CONCLUSION: It is, therefore, imperative to encourage the adoption of healthy lifestyles, especially in the peri-conception and interpregnancy periods. Likewise, there must be support in the multidisciplinary monitoring of these pregnant women to minimize associated complication rates.


Asunto(s)
Complicaciones del Embarazo , Humanos , Embarazo , Femenino , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/etiología , Recién Nacido , Obesidad/complicaciones , Obesidad/epidemiología , Efectos Tardíos de la Exposición Prenatal , Resultado del Embarazo/epidemiología , Obesidad Materna/complicaciones , Obesidad Materna/epidemiología , Diabetes Gestacional/epidemiología , Anomalías Congénitas/epidemiología , Anomalías Congénitas/etiología
5.
Nutr Health ; : 2601060241248716, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38650585

RESUMEN

Aim: To assess the effect of cashew nut flour on the hematological parameters of children living with HIV-AIDS. Method: A 32-week randomized, blind clinical trial conducted at a specialized outpatient clinic. Children aged 2-12 years were allocated to intervention groups (IGs) (n = 11) receiving 12 g/day of cashew nut flour and control groups (CGs) (n = 9) receiving 12 g/day of carboxymethyl cellulose. Parameters of erythrocytes, leukocytes, platelets, and lipid profiles were evaluated. Results: In the IG, the elevation and reduction of leukocyte and lipid profile biomarkers, respectively, were not statistically significant (p > 0.05). A clinically and statistically significant increase in mean corpuscular hemoglobin concentration was observed in the CG (p = 0.018), with a large effect size (Cohen's d = 0.9). There were no statistically significant changes in platelet counts among participants (p = 0.18). The effect size for white blood cell count, low-density lipoprotein cholesterol, very low-density lipoprotein, and triglycerides was moderate in the IG compared to the CG. Conclusion: Cashew nut flour supplementation may increase levels of leukocytes and lipid profile parameters in children living with HIV. Brazilian Clinical Trials Registry (REBEC): U1111.1276.6591.

6.
Matern Child Nutr ; : e13672, 2024 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-38853145

RESUMEN

This study aimed to investigate if the duration of breastfeeding and the method at initiation of complementary feeding affect eating behaviour in children aged 3-6 years. This is a cross-sectional analysis from the Childhood Obesity Risk Assessment Longitudinal Study project, an ongoing longitudinal cohort study that aims to identify childhood obesity risk factors in Spanish children. A total of 1215 children aged 3-6 years were included. Breastfeeding duration and the method of initiation of complementary feeding [baby-led weaning (BLW), traditional/spoon or mixed method] were evaluated. Eating behaviour at 3-6 years was assessed with the Child Eating Behaviour Questionnaire. Generalized linear models were fitted to assess the association between the aforementioned exposures and eating behaviour. Children breastfed for ≥4 months were less likely to be fussy eaters at 3-6 years compared to those breastfed for <1 month (OR: 0.86 95% CI: 0.76-0.98; p = 0.031). Compared to those children using the traditional/spoon-feeding method, those initiating complementary feeding through BLW or through a mixed approach were more likely to have higher scores on the enjoyment of food (EF) (OR, 95% CI: 1.33, 1.13-1.57; p = 0.001 and 1.17, 1.05-1.30; p = 0.002, respectively) and lower scores on food fussiness (FF) at 3-6 years (0.76, 0.62-0.91; p = 0.004 and 0.87, 0.78-0.98; p = 0.033, respectively). Breastfeeding for ≥4 months and initiation of complementary feeding with the BLW and a mixed approach were associated with greater EF and lower FF, which should endure practice.

7.
Eur J Health Law ; 31(3): 312-335, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38653475

RESUMEN

Mental health legislation is a cornerstone to ensure that individuals with severe mental illness access proper care and treatment. Each country establishes their own legislation. We aimed to compare the Portuguese and Irish Mental Health Acts (MHAs). We reviewed the respective MHA and the literature. While the definition of mental disorder is similar in general, who, where, when and how one can be detained differ. Judges decide on detentions in Portugal, while consultant psychiatrists may do so in Ireland. Community-based compulsory treatment is possible and used in Portugal while it is not possible in Ireland. Pros and cons of each approach are discussed with a reflection on the protection of human rights. Further theoretical and empirical studies comparing systems in different jurisdictions would be helpful to deepen our understanding of the legislation and guide on how to better serve individuals with severe mental illness.


Asunto(s)
Internamiento Obligatorio del Enfermo Mental , Trastornos Mentales , Humanos , Portugal , Irlanda , Internamiento Obligatorio del Enfermo Mental/legislación & jurisprudencia , Trastornos Mentales/terapia , Salud Mental/legislación & jurisprudencia , Derechos Humanos/legislación & jurisprudencia , Servicios de Salud Mental/legislación & jurisprudencia
8.
J Relig Health ; 63(2): 1623-1641, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38055143

RESUMEN

This study aims to adapt and validate the Religious and Spiritual Struggles Scale for the Portuguese population. The sample consisted of 732 participants with various religious affiliations. The exploratory factor analysis showed that it consists of six dimensions, similar to the initial instrument. A KMO of 0.91 was obtained. The confirmatory factor analysis confirmed the existence of six factors and showed adequate fit indices. Internal consistency and construct reliability were above 0.70. The analysis of the psychometric qualities of this instrument indicates that it can be applied to the Portuguese population and is a valuable instrument for psychotherapeutic practice and studies in the psychology of religion and spirituality.


Asunto(s)
Religión , Espiritualidad , Humanos , Reproducibilidad de los Resultados , Portugal , Etnicidad , Psicometría , Encuestas y Cuestionarios
9.
J Relig Health ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38955961

RESUMEN

The main aim of this study was to validate and adapt the Centrality of Religiosity Scale to the Portuguese population. A total of 1018 subjects participated in this study. The metric qualities demonstrated in the analyses suggested that the factor structure was based on five dimensions identical to those proposed by its authors. After analysing its psychometric qualities, we concluded that this instrument can be applied to the Portuguese population and is a valuable tool in studies related to the psychology of religion and spirituality.

10.
Omega (Westport) ; : 302228241259647, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38844415

RESUMEN

Background: Research has predominantly focused on the post-traumatic consequences of grief. Less is known about the factors associated with the capacity for recovery and growth. Objective: The main goal of this study is to analyse the mediating role of coping strategies in the relationship between the impact of the event and posttraumatic growth, considering the degree of kinship and the cause of death. Methods: This exploratory and correlational study, which used a cross-sectional design, involved a community sample of 889 adults who had lost a loved one. Results: Emotion and problem-focused coping strategies mediate the relationship between the impact of loss and posttraumatic growth, specifically when a spouse or a child dies. Conclusions: Individuals who experience greater suffering also undergo higher levels of post-traumatic growth. Coping strategies are crucial in post-trauma reconstruction and growth. Furthermore, the degree of kinship and the cause of death are decisive factors.

11.
J Proteome Res ; 22(9): 2995-3008, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37606915

RESUMEN

Autoimmune diseases (AID), such as systemic lupus erythematosus (SLE) and systemic sclerosis (SS), are complex conditions involving immune system dysregulation. Diagnosis is challenging, requiring biomarkers for improved detection and prediction of relapses. Lipids have emerged as potential biomarkers due to their role in inflammation and immune response. This study uses an untargeted C18 RP-LC-MS lipidomics approach to comprehensively assess changes in lipid profiles in patients with SLE and SS. By analyzing whole blood and plasma, the study aims to simplify the lipidomic analysis, explore cellular-level lipids, and compare lipid signatures of SLE and SS with healthy controls. Our findings showed variations in the lipid profile of SLE and SS. Sphingomyelin and ceramide molecular species showed significant increases in plasma samples from SS patients, suggesting an atherosclerotic profile and potentially serving as lipid biomarkers. Phosphatidylserine species in whole blood from SLE patients exhibited elevated levels supporting previously reported dysregulated processes of cell death and defective clearance of dying cells in this AID. Moreover, decreased phospholipids bearing PUFA were observed, potentially attributed to the degradation of these species through lipid peroxidation processes. Further studies are needed to better understand the role of lipids in the pathological mechanisms underlying SLE and SS.

12.
Neurochem Res ; 48(11): 3447-3456, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37464227

RESUMEN

Evidence indicates that transcranial direct current stimulation (tDCS) provides therapeutic benefits in different situations, such as epilepsy, depression, inflammatory and neuropathic pain. Despite the increasing use of tDCS, its cellular and molecular basis remains unknown. Astrocytes display a close functional and structural relationship with neurons and have been identified as mediators of neuroprotection in tDCS. Considering the importance of hippocampal glutamatergic neurotransmission in nociceptive pathways, we decided to investigate short-term changes in the hippocampal astrocytes of rats subjected to tDCS, evaluating specific cellular markers (GFAP and S100B), as well as markers of astroglial activity; glutamate uptake, glutamine synthesis by glutamine synthetase (GS) and glutathione content. Data clearly show that a single session of tDCS increases the pain threshold elicited by mechanical and thermal stimuli, as evaluated by von Frey and hot plate tests, respectively. These changes involve inflammatory and astroglial neurochemical changes in the hippocampus, based on specific changes in cell markers, such as S100B and GS. Alterations in S100B were also observed in the cerebrospinal fluid of tDCS animals and, most importantly, specific functional changes (increased glutamate uptake and increased GS activity) were detected in hippocampal astrocytes. These findings contribute to a better understanding of tDCS as a therapeutic strategy for nervous disorders and reinforce the importance of astrocytes as therapeutic targets.


Asunto(s)
Epilepsia , Estimulación Transcraneal de Corriente Directa , Ratas , Animales , Astrocitos/metabolismo , Hipocampo/metabolismo , Epilepsia/metabolismo , Ácido Glutámico/metabolismo , Glutamato-Amoníaco Ligasa/metabolismo
13.
Br J Nutr ; 130(7): 1155-1166, 2023 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-36722158

RESUMEN

This study aims to evaluate the association between Dietary Total Antioxidant Capacity (dTAC) and Total Antioxidant Capacity of food groups (fgTAC) with the incidence of depression in Brazilian graduates participating in the Cohort of Universities of Minas Gerais (CUME Study). The sample consisted of 2572 participants without a medical diagnosis of depression at baseline who responded to at least one follow-up questionnaire from the CUME Project. The Ferric Reducing Antioxidant Power assay was used to determine dTAC. Incidence of depression was estimated by self-reported medical diagnosis of depression during the years of cohort follow-up. Cox regression models were used to relate dTAC and fgTAC to the incidence of depression. The mean follow-up time was 2·96 (1·00) years, and 246 cases of depression were observed (32·3/1000 person-years). The mean dTAC was 11·03 (4·84) mmol/d. We found no associations between higher dTAC and lower risk of developing depression after adjusting for possible confounders. The incidence of depression was inversely associated with fgTAC of the beans and lentils group (hazard ratio (HR): 0·61; 95 % CI 0·41, 0·90). The fgTAC of the junk food group was positively associated with higher incidence of depression after all adjustments (HR: 1·57; 95 % CI 1·08, 2·26). Our findings do not support an association between dTAC and the incidence of depression in a highly educated Brazilian population. However, associations of fgTAC show the importance of analysing the food matrix in which these antioxidants are inserted. We highlight the need for more prospective studies with different nationalities to confirm these results.


Asunto(s)
Antioxidantes , Depresión , Humanos , Antioxidantes/análisis , Brasil/epidemiología , Incidencia , Estudios Prospectivos , Depresión/epidemiología , Dieta
14.
Eur J Nutr ; 62(3): 1109-1121, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36681744

RESUMEN

PURPOSE: This paper aims to present an overview of the definitions of "plant-based and "vegetarian diets" adopted by different organizations worldwide, proposing new standard definitions and discussing the notion of vegetarianism as a restrictive dietary pattern. METHODS: An extensive literature review on the different definitions of vegetarian and plant-based diets was conducted. Definitions of different international vegetarian and vegan organizations were also taken into account. Objective definitions for vegetarian and plant-based diets, as well as for their subcategories, were proposed. Other aspects related to how vegetarian diets are viewed and defined were also discussed. RESULTS: We proposed that a vegetarian diet should be defined as "a dietary pattern that excludes meat, meat-derived foods, and, to different extents, other animal products". This definition would include, among others, ovolactovegetarian and vegan diets. The proposed definition for a plant-based diet was "a dietary pattern in which foods of animal origin are totally or mostly excluded". Other types of diets, such as flexitarian and pescetarian diets, could be considered plant-based. A vegetarian diet should not be considered restrictive. Instead, terms such as alternative or non-conventional could be used to define it and to distinguish it from the conventional diet adopted by most of the Western population. CONCLUSION: This paper was able to elaborate objective definitions of vegetarian and plant-based diets. Standardizing nomenclatures may reduce misinterpretation and confusion in this field of study.


Asunto(s)
Dieta Vegetariana , Dieta , Animales , Humanos , Dieta Vegana , Vegetarianos , Carne
15.
Neurol Sci ; 44(5): 1831-1832, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36781565

RESUMEN

A 43-year-old male patient with a 7-year history of liver transplantation due to p.Val50Met hereditary transthyretin amyloidosis (ATTRv) persisted with refractory neuropathic pain, distal weakness, and progressive worsening of dysautonomia. Nerve ultrasound was performed showing increased nerve cross-sectional area and enlarged fascicles in proximal sites in both arms, suggestive of amyloidosis. Nerve enlargement is commonly reported in inflammatory and hereditary demyelinating hypertrophic neuropathies but can also be present in deposition diseases. Neuromuscular ultrasound is a tool for the bed-side assessment of peripheral neuropathies and it is useful for early diagnosis of ATTRv.


Asunto(s)
Neuropatías Amiloides Familiares , Neuralgia , Masculino , Humanos , Adulto , Neuropatías Amiloides Familiares/complicaciones , Neuropatías Amiloides Familiares/diagnóstico por imagen , Ultrasonografía , Prealbúmina
16.
Oral Dis ; 29(7): 2854-2864, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35785457

RESUMEN

OBJECTIVE: To compare the accuracy of periodontal examination at 6-sites full-mouth protocol with clinical and radiographic partial-mouth recording protocols (PRPs) to diagnose periodontitis considering new 2018 case definition. METHODS: Periodontitis was diagnosed by full-mouth assessment of clinical attachment level (CAL) at 6-sites (n = 8529) according to 2018 case definition (standard reference). Three clinical and radiographic PRPs were considered: (i) 4 interproximal sites of all teeth (4-sites, full-mouth); (ii) 6-sites on Community Periodontal Index of Treatment Needs (CPITN) teeth (6-sites, CPITN teeth); (iii) 4-sites on CPITN teeth (4-sites, CPITN teeth); (iv) radiographic examination on interproximal sites of all teeth (rM-D, full-mouth); and (v) radiographic examination on interproximal sites of CPITN teeth (rM-D, CPITN teeth) using Image J®. Sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV), accuracy, and Κappa (k) were estimated (α = 0.05). RESULTS: The 4-sites, full-mouth protocol showed 100% sensitivity and NPV, 79.87% PPV, low specificity (38.32%), 69.30% accuracy, and poor agreement (k = 0.468). 6-sites and 4-sites CPITN teeth protocols showed 100% PPV and specificity, sensitivity and NPV of >60%, accuracy of >80%, and good agreement (k > 0.65). All clinical PRPs outperformed radiographic protocols. CONCLUSION: Clinical PRPs using index teeth are highly accurate in diagnosing periodontitis considering 2018 case definition.


Asunto(s)
Periodontitis , Diente , Humanos , Periodontitis/diagnóstico por imagen , Valor Predictivo de las Pruebas
17.
Oral Dis ; 29(8): 3630-3639, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35716346

RESUMEN

OBJECTIVE: To investigate the association between insulin resistance markers and periodontitis in adolescents, analyzing confounder variables and the adiposity as a mediator. METHODS: This is population-based study is representative of adolescents aged 17-18 years from public schools in São Luís, Brazil (n = 405). Insulin resistance was assessed using the Model of Assessment of the Homeostasis of the Insulin Resistance Index (HOMA-IR) and its percussor triglycerides/HDL-cholesterol ratio (TG/HDL-c). The outcome was Initial Periodontitis, a latent variable estimated by the common variance shared among bleeding on probing, probing depth ≥ 4 mm, and clinical attachment loss ≥ 4 mm. The association between insulin resistance and Initial Periodontitis was modeled via pathways triggered by socioeconomic status, smoking, alcohol, and Adiposity, using structural equation modeling. RESULTS: Higher TG/HDL-c was directly associated with higher Initial Periodontitis (standardized coefficient [SC] = 0.130, p < 0.001). HOMA-IR was not associated with periodontal outcome (SC = 0.023, p = 0.075), but it was with Adiposity (SC = 0.495, p < 0.001). Higher TG/HDL-c was associated with Adiposity (SC = 0.202, p < 0.001). CONCLUSION: The insulin resistance markers were associated with early signs of periodontal breakdown among adolescents, suggesting a possible relationship between diabetes and periodontitis commences early in life.


Asunto(s)
Diabetes Mellitus , Resistencia a la Insulina , Periodontitis , Humanos , Adolescente , HDL-Colesterol , Obesidad , Triglicéridos , Periodontitis/complicaciones
18.
Mar Drugs ; 21(3)2023 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-36976232

RESUMEN

Brown macroalgae are an important source of polysaccharides, mainly fucose-containing sulphated polysaccharides (FCSPs), associated with several biological activities. However, the structural diversity and structure-function relationships for their bioactivities are still undisclosed. Thus, the aim of this work was to characterize the chemical structure of water-soluble Saccharina latissima polysaccharides and evaluate their immunostimulatory and hypocholesterolemic activities, helping to pinpoint a structure-activity relationship. Alginate, laminarans (F1, neutral glucose-rich polysaccharides), and two fractions (F2 and F3) of FCSPs (negatively charged) were studied. Whereas F2 is rich in uronic acids (45 mol%) and fucose (29 mol%), F3 is rich in fucose (59 mol%) and galactose (21 mol%). These two fractions of FCSPs showed immunostimulatory activity on B lymphocytes, which could be associated with the presence of sulphate groups. Only F2 exhibited a significant effect in reductions in in vitro cholesterol's bioaccessibility attributed to the sequestration of bile salts. Therefore, S. latissima FCSPs were shown to have potential as immunostimulatory and hypocholesterolemic functional ingredients, where their content in uronic acids and sulphation seem to be relevant for the bioactive and healthy properties.


Asunto(s)
Laminaria , Phaeophyceae , Fucosa/química , Agua , Phaeophyceae/química , Polisacáridos/farmacología , Polisacáridos/química , Sulfatos , Ácidos Urónicos
19.
Proc Natl Acad Sci U S A ; 117(12): 6741-6751, 2020 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-32152117

RESUMEN

Neurodegenerative diseases feature specific misfolded or misassembled proteins associated with neurotoxicity. The precise mechanisms by which protein aggregates first arise in the majority of sporadic cases have remained unclear. Likely, a first critical mass of misfolded proteins starts a vicious cycle of a prion-like expansion. We hypothesize that viruses, having evolved to hijack the host cellular machinery for catalyzing their replication, lead to profound disturbances of cellular proteostasis, resulting in such a critical mass of protein aggregates. Here, we investigated the effect of influenza virus (H1N1) strains on proteostasis of proteins associated with neurodegenerative diseases in Lund human mesencephalic dopaminergic cells in vitro and infection of Rag knockout mice in vivo. We demonstrate that acute H1N1 infection leads to the formation of α-synuclein and Disrupted-in-Schizophrenia 1 (DISC1) aggregates, but not of tau or TDP-43 aggregates, indicating a selective effect on proteostasis. Oseltamivir phosphate, an antiinfluenza drug, prevented H1N1-induced α-synuclein aggregation. As a cell pathobiological mechanism, we identified H1N1-induced blocking of autophagosome formation and inhibition of autophagic flux. In addition, α-synuclein aggregates appeared in infected cell populations connected to the olfactory bulbs following intranasal instillation of H1N1 in Rag knockout mice. We propose that H1N1 virus replication in neuronal cells can induce seeds of aggregated α-synuclein or DISC1 that may be able to initiate further detrimental downstream events and should thus be considered a risk factor in the pathogenesis of synucleinopathies or a subset of mental disorders. More generally, aberrant proteostasis induced by viruses may be an underappreciated factor in initiating protein misfolding.


Asunto(s)
Proteínas de Homeodominio/fisiología , Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Gripe Humana/complicaciones , Infecciones por Orthomyxoviridae/complicaciones , Proteostasis , Sinucleinopatías/etiología , alfa-Sinucleína/química , Animales , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/patología , Femenino , Humanos , Gripe Humana/virología , Ratones , Ratones Noqueados , Proteínas del Tejido Nervioso/metabolismo , Infecciones por Orthomyxoviridae/virología , Multimerización de Proteína , Sinucleinopatías/metabolismo , Sinucleinopatías/patología , alfa-Sinucleína/metabolismo
20.
Int J Mol Sci ; 24(4)2023 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-36834764

RESUMEN

The use of viral vectors as therapeutic products for multiple applications such as vaccines, cancer treatment, or gene therapies, has been growing exponentially. Therefore, improved manufacturing processes are needed to cope with the high number of functional particles required for clinical trials and, eventually, commercialization. Affinity chromatography (AC) can be used to simplify purification processes and generate clinical-grade products with high titer and purity. However, one of the major challenges in the purification of Lentiviral vectors (LVs) using AC is to combine a highly specific ligand with a gentle elution condition assuring the preservation of vector biological activity. In this work, we report for the first time the implementation of an AC resin to specifically purify VSV-G pseudotyped LVs. After ligand screening, different critical process parameters were assessed and optimized. A dynamic capacity of 1 × 1011 total particles per mL of resin was determined and an average recovery yield of 45% was found for the small-scale purification process. The established AC robustness was confirmed by the performance of an intermediate scale providing an infectious particles yield of 54%, which demonstrates the scalability and reproducibility of the AC matrix. Overall, this work contributes to increasing downstream process efficiency by delivering a purification technology that enables high purity, scalability, and process intensification in a single step, contributing to time-to-market reduction.


Asunto(s)
Vectores Genéticos , Lentivirus , Lentivirus/genética , Ligandos , Reproducibilidad de los Resultados , Terapia Genética/métodos
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