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1.
J Texture Stud ; 55(5): e12866, 2024 Oct.
Article de Anglais | MEDLINE | ID: mdl-39261281

RÉSUMÉ

Fruit texture is a priority trait that guarantees the long-term economic sustainability of the cranberry industry through value-added products such as sweetened dried cranberries (SDCs). To develop a standard methodology to measure texture, we conducted a comparative analysis of 22 textural traits using five different methods under both harvest and postharvest conditions in 10 representative cranberry cultivars. A set of textural traits from the 10%-strain compression and puncture methods were identified that differentiate between cultivars primarily based on hardness/stiffness and elasticity properties. The complementary use of both methodologies allowed for a detailed evaluation by capturing the effect of key texture-determining factors such as structure, flesh, and skin. Furthermore, the high effectiveness of this approach in different conditions and its ability to capture high phenotypic variation in cultivars highlights its great potential for applicability in various areas of the value chain and research. Therefore, this study provides an informed reference for unifying future efforts to enhance cranberry fruit texture and quality.


Sujet(s)
Fruit , Vaccinium macrocarpon , Dureté , Élasticité
2.
JAMA Netw Open ; 7(9): e2431115, 2024 Sep 03.
Article de Anglais | MEDLINE | ID: mdl-39230905

RÉSUMÉ

Importance: Data on the performance of traumatic brain injury (TBI) biomarkers within minutes of injury are lacking. Objectives: To examine the performance of glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and microtubule-associated protein 2 (MAP-2) within 30 and 60 minutes of TBI in identifying intracranial lesions on computed tomography (CT) scan, need for neurosurgical intervention (NSI), and clinically important early outcomes (CIEO). Design, Setting, and Participants: This cohort study is a biomarker analysis of a multicenter prehospital TBI cohort from the Prehospital Tranexamic Acid Use for TBI clinical trial conducted across 20 centers and 39 emergency medical systems in North America from May 2015 to March 2017. Prehospital hemodynamically stable adult patients with traumatic injury and suspected moderate to severe TBI were included. Blood samples were measured for GFAP, UCH-L1, and MAP-2. Data were analyzed from December 1, 2023, to March 15, 2024. Main Outcomes and Measures: The presence of CT lesions, diffuse injury severity on CT, NSI within 24 hours of injury, and CIEO (composite outcome including early death, neurosurgery, or prolonged mechanical ventilation ≥7 days) within 7 days of injury. Results: Of 966 patients enrolled, 804 patients (mean [SD] age, 41 [19] years; 418 [74.2%] male) had blood samples, including 563 within 60 minutes and 375 within 30 minutes of injury. Among patients with blood drawn within 30 minutes of injury, 212 patients (56.5%) had CT lesions, 61 patients (16.3%) had NSI, and 112 patients (30.0%) had CIEO. Among those with blood drawn within 60 minutes, 316 patients (56.1%) had CT lesions, 95 patients (16.9%) had NSI, and 172 patients (30.6%) had CIEO. All biomarkers showed significant elevations with worsening diffuse injury on CT within 30 and 60 minutes of injury. Among blood samples taken within 30 minutes, GFAP had the highest area under the receiver operating characteristic curve (AUC) to detect CT lesions, at 0.88 (95% CI, 0.85-0.92), followed by MAP-2 (AUC, 0.78; 95% CI, 0.73-0.83) and UCH-L1 (AUC, 0.75; 95% CI, 0.70-0.80). Among blood samples taken within 60 minutes, AUCs for CT lesions were 0.89 (95% CI, 0.86-0.92) for GFAP, 0.76 (95% CI, 0.72-0.80) for MAP-2, and 0.73 (95% CI, 0.69-0.77) for UCH-L1. Among blood samples taken within 30 minutes, AUCs for NSI were 0.78 (95% CI, 0.72-0.84) for GFAP, 0.75 (95% CI, 0.68-0.81) for MAP-2, and 0.69 (95% CI, 0.63-0.75) for UCH-L1; and for CIEO, AUCs were 0.89 (95% CI, 0.85-0.93) for GFAP, 0.83 (95% CI, 0.78-0.87) for MAP-2, and 0.77 (95% CI, 0.72-0.82) for UCH-L1. Combining the biomarkers was no better than GFAP alone for all outcomes. At GFAP of 30 pg/mL within 30 minutes, sensitivity for CT lesions was 98.1% (95% CI, 94.9%-99.4%) and specificity was 34.4% (95% CI, 27.2%-42.2%). GFAP levels greater than 6200 pg/mL were associated with high risk of NSI and CIEO. Conclusions and Relevance: In this cohort study of prehospital patients with TBI, GFAP, UCH-L1, and MAP-2 measured within 30 and 60 minutes of injury were significantly associated with traumatic intracranial lesions and diffuse injury severity on CT scan, 24-hour NSI, and 7-day CIEO. GFAP was the strongest independent marker associated with all outcomes. This study sets a precedent for the early utility of GFAP in the first 30 minutes from injury in future clinical and research endeavors.


Sujet(s)
Marqueurs biologiques , Lésions traumatiques de l'encéphale , Protéine gliofibrillaire acide , Protéines associées aux microtubules , Ubiquitin thiolesterase , Humains , Lésions traumatiques de l'encéphale/sang , Ubiquitin thiolesterase/sang , Mâle , Femelle , Adulte , Protéine gliofibrillaire acide/sang , Adulte d'âge moyen , Marqueurs biologiques/sang , Protéines associées aux microtubules/sang , Tomodensitométrie , Études de cohortes , Facteurs temps
3.
Knee ; 51: 44-57, 2024 Sep 04.
Article de Anglais | MEDLINE | ID: mdl-39236637

RÉSUMÉ

INTRODUCTION: This study aimed to evaluate the effectiveness and safety of a combined surgical approach for treating complex patellofemoral instability. This approach combines four procedures: medial patellofemoral ligament (MPFL) reconstruction with the quasi-anatomic technique, lateral retinaculum release, anteromedialization and distalization of tibial tuberosity and patellar/femoral mosaicplasty. MATERIAL AND METHODS: Between August and November 2021, we enrolled 27 patients in the study (21 females, 6 males, average age 28.6 years). All with patella alta, recurrent patellar instability, severe cartilage focal damage, and increased tibial tubercle-trochlear groove distance. All underwent the combined procedure during this period. We assessed their pain and functional scores before surgery and at 6, 12, and 24 months after surgery using standardized scoring systems. RESULTS: Patients initially reported significant pain and functional limitations. However, at 24 months, their pain scores significantly reduced, averaging 1.5 compared to 8.2 pre-surgery. Similarly, their functional scores substantially improved, with Lysholm, Tegner, Kujala, BPII scores reaching 87.44, 8.44, 90.03, 86.07 compared to 56.4, 3.7, 42.48, 23 pre-surgery, respectively. Importantly, no cases of recurrent instability occurred, and 96.3% of patients reported complete satisfaction. CONCLUSIONS: This combined surgical approach has a high rate of success for patients with patella alta, recurrent lateral patellar instability, severe focal chondral lesions, and increased TT-TG distance. Moreover, 26 out of 27 patients (96.3%) reported total satisfaction. Therefore, we conclude that although this procedure combination is not simple, it is a safe, reproducible, and alleviates pain at 24 months postoperatively, and significantly improves functional scores.

4.
Article de Anglais | MEDLINE | ID: mdl-39218714

RÉSUMÉ

Pheochromocytomas and paragangliomas are rare neuroendocrine tumours. Around 20-25 % of patients develop metastases, for which there is an urgent need of prognostic markers and therapeutic stratification strategies. The presence of a MAML3-fusion is associated with increased metastatic risk, but neither the processes underlying disease progression, nor targetable vulnerabilities have been addressed. We have compiled a cohort of 850 patients, which has shown a 3.65 % fusion prevalence and represents the largest MAML3-positive series reported to date. While MAML3-fusions mainly cause single pheochromocytomas, we also observed somatic post-zygotic events, resulting in multiple tumours in the same patient. MAML3-tumours show increased expression of neuroendocrine-to-mesenchymal transition markers, MYC-targets, and angiogenesis-related genes, leading to a distinct tumour microenvironment with unique vascular and immune profiles. Importantly, our findings have identified MAML3-tumours specific vulnerabilities beyond Wnt-pathway dysregulation, such as a rich vascular network, and overexpression of PD-L1 and CD40, suggesting potential therapeutic targets.

5.
J Dent Anesth Pain Med ; 24(4): 227-243, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-39118815

RÉSUMÉ

This study aimed to evaluate pain assessment strategies and factors associated with outcomes after microvascular decompression for the treatment of primary trigeminal neuralgia in adults. We conducted a systematic review and meta-analysis of English, Spanish, and French literature. We searched three databases, PubMed, Ovid, and EBSCO, from 2010 to 2022 and selected studies including patients with primary trigeminal neuralgia, clear pain assessment, and pain outcomes. Population means and standard deviations were calculated. Studies that included factors associated with postoperative outcomes were included in the meta-analysis. A total of 995 studies involving 5673 patients with primary trigeminal neuralgia following microvascular decompression were included. Patients with arteries compressing the trigeminal nerve demonstrated optimal outcomes following microvascular decompression (odds ratio [OR]= 0.39; 95% confidence interval [CI] = 0.19-0.80; X2 = 46.31; Dof = 15; I2 = 68%; P = < 0.0001). Conversely, when comparing arterial vs venous compression of the trigeminal nerve (OR = 2.72; 95% CI = 1.16-6.38; X2 = 23.23; Dof = 10; I2 = 57%; P = 0.01), venous compression demonstrated poor outcomes after microvascular decompression. Additionally, when comparing single-vessel vs multiple-vessel compression (OR = 2.72; 95% CI = 1.18-6.25; X2 = 21.17; Dof = 9; I2 = 57%; P = 0.01), patients demonstrated unfavorable outcomes after microvascular decompression. This systematic review and meta-analysis evaluated factors associated with outcomes following microvascular decompression (MVD) for primary trigeminal neuralgia (PTN). Although MVD is an optimal treatment strategy for PTN, a gap exists in interpreting the results when considering the lack of evidence for most pain assessment strategies.

6.
Glia ; 2024 Aug 26.
Article de Anglais | MEDLINE | ID: mdl-39188024

RÉSUMÉ

Astrocytes play a multifaceted role regulating brain glucose metabolism, ion homeostasis, neurotransmitters clearance, and water dynamics being essential in supporting synaptic function. Under different pathological conditions such as brain stroke, epilepsy, and neurodegenerative disorders, excitotoxicity plays a crucial role, however, the contribution of astrocytic activity in protecting neurons from excitotoxicity-induced damage is yet to be fully understood. In this work, we evaluated the effect of astrocytic activation by Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) on brain glucose metabolism in wild-type (WT) mice, and we investigated the effects of sustained astrocyte activation following an insult induced by intrahippocampal (iHPC) kainic acid (KA) injection using 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) positron emission tomography (PET) imaging, along with behavioral test, nuclear magnetic resonance (NMR) spectroscopy and histochemistry. Astrocytic Ca2+ activation increased the 18F-FDG uptake, but this effect was not found when the study was performed in knock out mice for type-2 inositol 1,4,5-trisphosphate receptor (Ip3r2-/-) nor in floxed mice to abolish glucose transporter 1 (GLUT1) expression in hippocampal astrocytes (GLUT1ΔGFAP). Sustained astrocyte activation after KA injection reversed the brain glucose hypometabolism, restored hippocampal function, prevented neuronal death, and increased hippocampal GABA levels. The findings of our study indicate that astrocytic GLUT1 function is crucial for regulating brain glucose metabolism. Astrocytic Ca2+ activation has been shown to promote adaptive changes that significantly contribute to mitigating the effects of KA-induced damage. This evidence suggests a protective role of activated astrocytes against KA-induced excitotoxicity.

7.
Healthcare (Basel) ; 12(16)2024 Aug 08.
Article de Anglais | MEDLINE | ID: mdl-39201134

RÉSUMÉ

OBJECTIVES: To analyse the influence of the COVID-19 pandemic on the development of anxiety in nursing students and the factors involved. DESIGN: A systematic review and meta-analysis. DATA SOURCE: PubMed, CINAHL, Scopus and Web of Science. BACKGROUND: Nursing students are at an increased risk of developing mental overload, due to the presence of many sources of stress during their academic training. Therefore, the COVID-19 pandemic has had an impact on the mental health of the general population, especially on healthcare workers and consequently on students undertaking placements in healthcare settings. METHODS: A systematic review was conducted using PubMed, CINAHL, Scopus and Web of Science databases. A total of 24 articles were included in the review, and 20 articles were selected for the meta-analysis. RESULTS: We found that the anxiety scores of nursing students during the COVID-19 pandemic were slightly higher (50%) than before the pandemic. The most influential risk factors for developing anxiety were academics, age, gender, having children, living in urban areas or with family, having an addiction to social networks, and having a fear of becoming infected with COVID-19. Resilience, spiritual support and feelings of happiness protected students against the risk of developing high levels of anxiety. CONCLUSIONS: The COVID-19 pandemic has led to increased levels of anxiety in nursing students. Thirty-five percent of the meta-analytically analysed sample had elevated levels of anxiety.

8.
Clin Sci (Lond) ; 138(17): 1071-1087, 2024 Sep 04.
Article de Anglais | MEDLINE | ID: mdl-39136472

RÉSUMÉ

Perivascular adipose tissue (PVAT) negatively regulates vascular muscle contraction. However, in the context of obesity, the PVAT releases vasoconstrictor substances that detrimentally affect vascular function. A pivotal player in this scenario is the peptide endothelin-1 (ET-1), which induces oxidative stress and disrupts vascular function. The present study postulates that obesity augments ET-1 production in the PVAT, decreases the function of the nuclear factor erythroid 2-related factor-2 (Nrf2) transcription factor, further increasing reactive oxygen species (ROS) generation, culminating in PVAT dysfunction. Male C57BL/6 mice were fed either a standard or a high-fat diet for 16 weeks. Mice were also treated with saline or a daily dose of 100 mg·kg-1 of the ETA and ETB receptor antagonist Bosentan, for 7 days. Vascular function was evaluated in thoracic aortic rings, with and without PVAT. Mechanistic studies utilized PVAT from all groups and cultured WT-1 mouse brown adipocytes. PVAT from obese mice exhibited increased ET-1 production, increased ECE1 and ETA gene expression, loss of the anticontractile effect, as well as increased ROS production, decreased Nrf2 activity, and downregulated expression of Nrf2-targeted antioxidant genes. PVAT of obese mice also exhibited increased expression of Tyr216-phosphorylated-GSK3ß and KEAP1, but not BACH1 - negative Nrf2 regulators. Bosentan treatment reversed all these effects. Similarly, ET-1 increased ROS generation and decreased Nrf2 activity in brown adipocytes, events mitigated by BQ123 (ETA receptor antagonist). These findings place ET-1 as a major contributor to PVAT dysfunction in obesity and highlight that pharmacological control of ET-1 effects restores PVAT's cardiovascular protective role.


Sujet(s)
Tissu adipeux , Régulation négative , Endothéline-1 , Souris de lignée C57BL , Facteur-2 apparenté à NF-E2 , Obésité , Espèces réactives de l'oxygène , Animaux , Endothéline-1/métabolisme , Obésité/métabolisme , Obésité/physiopathologie , Mâle , Tissu adipeux/métabolisme , Facteur-2 apparenté à NF-E2/métabolisme , Espèces réactives de l'oxygène/métabolisme , Bosentan/pharmacologie , Alimentation riche en graisse , Souris , Stress oxydatif , Récepteur de type A de l'endothéline/métabolisme , Récepteur de type A de l'endothéline/génétique , Enzymes de conversion de l'endothéline/métabolisme , Aorte thoracique/métabolisme , Aorte thoracique/effets des médicaments et des substances chimiques , Aorte thoracique/physiopathologie
9.
Org Biomol Chem ; 22(35): 7240-7244, 2024 09 11.
Article de Anglais | MEDLINE | ID: mdl-39171544

RÉSUMÉ

A synthetic strategy for obtaining a new series of 1,5-disubstituted tetrazole-benzofuran hybrid systems via a one-pot five-component reaction is described. This process involves a Ugi-azide multicomponent reaction coupled to an intramolecular cyclization catalyzed by Pd/Cu, resulting in low to moderate yields from 21 to 67%. This protocol allowed the synthesis of highly substituted benzofurans at the 2-position through an operationally simple process under mild reaction conditions and with high bond forming efficiency due to the formation of six new bonds (two C-C, two C-N, one N-N, and one C-O). Besides, to evaluate the antifungal activity of 1,5-disubstituted tetrazole-benzofurans 9a-n, in vitro studies against Mucor lusitanicus were performed, finding that compound 9b exhibits bioactivity comparable to the commercial antifungal drug Amphotericin B. These results suggest potential for use in controlling mucormycosis infections in animal models, highlighting the importance of these findings given the limited antifungal drug options and high mortality rates associated with this infection.


Sujet(s)
Antifongiques , Benzofuranes , Tests de sensibilité microbienne , Mucor , Tétrazoles , Benzofuranes/pharmacologie , Benzofuranes/composition chimique , Benzofuranes/synthèse chimique , Mucor/effets des médicaments et des substances chimiques , Antifongiques/pharmacologie , Antifongiques/synthèse chimique , Antifongiques/composition chimique , Tétrazoles/pharmacologie , Tétrazoles/composition chimique , Tétrazoles/synthèse chimique , Relation structure-activité , Structure moléculaire
10.
Heliyon ; 10(15): e35752, 2024 Aug 15.
Article de Anglais | MEDLINE | ID: mdl-39170185

RÉSUMÉ

Brain glucose hypometabolism and insulin alterations are common features of many neurological diseases. Herein we sought to corroborate the brain glucose hypometabolism that develops with ageing in 12-months old Tau-VLW transgenic mice, a model of tauopathy, as well as to determine whether this model showed signs of altered peripheral glucose metabolism. Our results demonstrated that 12-old months Tau mice exhibited brain glucose hypometabolism as well as basal hyperglycemia, impaired glucose tolerance, hyperinsulinemia, and signs of insulin resistance. Then, we further studied the effect of chronic metformin treatment (9 months) in Tau-VLW mice from 9 to 18 months of age. Longitudinal PET neuroimaging studies revealed that chronic metformin altered the temporal profile in the progression of brain glucose hypometabolism associated with ageing. Besides, metformin altered the content and/or phosphorylation of key components of the insulin signal transduction pathway in the frontal cortex leading to significant changes in the content of the active forms. Thus, metformin increased the expression of pAKT-Y474 while reducing pmTOR-S2448 and pGSK3ß. These changes might be related, at least partially, to a slow progression of ageing, neurological damage, and cognitive decline. Metformin also improved the peripheral glucose tolerance and the ability of the Tau-VLW mice to maintain their body weight through ageing. Altogether our study shows that the tau-VLW mice could be a useful model to study the potential interrelationship between tauopathy and central and peripheral glucose metabolism alterations. More importantly our results suggest that chronic metformin treatment may have direct beneficial central effects by post-transcriptional modulation of key components of the insulin signal transduction pathway.

11.
Clin Drug Investig ; 44(8): 553-576, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-39085682

RÉSUMÉ

The use of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs), such as lorlatinib, for the treatment of patients with ALK gene rearrangement (or ALK-positive) non-small cell lung cancer (NSCLC) has been shown to improve the overall survival and quality of life of these patients. However, lorlatinib is not exempt from potential adverse events. Adequate monitoring and management of these adverse events are critical for increasing patient adherence to lorlatinib, thereby maximizing the benefits of treatment and minimizing the risks associated with treatment discontinuation. Considering that the adverse events of lorlatinib can affect different organs and systems, the participation of a multidisciplinary team, including cardiologists, neurologists, internal medicine specialists, and oncology pharmacists, is needed. This article presents specific and pragmatic strategies for identifying and treating the most relevant adverse events associated with lorlatinib in patients with advanced ALK-positive NSCLC based on the clinical experience of a multidisciplinary panel of experts.


Sujet(s)
Aminopyridines , Kinase du lymphome anaplasique , Carcinome pulmonaire non à petites cellules , Lactames macrocycliques , Lactames , Tumeurs du poumon , Pyrazoles , Humains , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , Carcinome pulmonaire non à petites cellules/génétique , Carcinome pulmonaire non à petites cellules/anatomopathologie , Tumeurs du poumon/traitement médicamenteux , Tumeurs du poumon/génétique , Tumeurs du poumon/anatomopathologie , Kinase du lymphome anaplasique/antagonistes et inhibiteurs , Kinase du lymphome anaplasique/génétique , Aminopyridines/effets indésirables , Pyrazoles/effets indésirables , Pyrazoles/usage thérapeutique , Inhibiteurs de protéines kinases/effets indésirables , Inhibiteurs de protéines kinases/usage thérapeutique , Consensus , Antinéoplasiques/effets indésirables , Antinéoplasiques/usage thérapeutique
12.
Antibiotics (Basel) ; 13(7)2024 Jun 27.
Article de Anglais | MEDLINE | ID: mdl-39061281

RÉSUMÉ

The prevalence of multidrug-resistant Gram-negative infections, particularly carbapenem-resistant strains, has become a significant global health concern. Ceftazidime-avibactam (CZA) has emerged as a promising treatment option. However, data on its efficacy and safety in children are scarce, necessitating further investigation. We conducted a descriptive case series at a tertiary hospital in Spain from February 2019 to January 2022. Pediatric patients (<16 years) treated with CZA for confirmed or suspected multidrug-resistant Gram-negative infections were included. The clinical and microbiological characteristics, treatment approaches, and outcomes were examined. Eighteen children received CZA treatment. All had complex chronic conditions, with the most frequent underlying main diseases being liver transplantation (n = 8) and biliary atresia (n = 4). The predominant type of infection for which they received CZA was intra-abdominal infection caused or suspected to be caused by OXA-48-producing Klebsiella pneumoniae. CZA was generally well tolerated. Within the first month of starting CZA therapy, two patients died, with one case directly linked to the infection's fatal outcome. Some patients needed repeated courses of therapy due to recurrent infections, yet no resistance development was noted. In summary, the use of CZA showed effectiveness and safety, while the lack of resistance development highlights CZA's potential as a primary treatment option against OXA-48-producing infections.

13.
Physiol Behav ; 284: 114649, 2024 Oct 01.
Article de Anglais | MEDLINE | ID: mdl-39069113

RÉSUMÉ

Puberty is a period of brain organization impacting the expression of social and sexual behaviors. Here, we assessed the effects of an acute pubertal stressor (immune challenge) on the expression of juvenile play (short-term) and sexual partner preference (long-term) in male rats. Juvenile play was assessed over ten trials at postnatal days (PND) (31-40) with age- and sex-matched conspecifics, and at PND35 males received a single injection of lipopolysaccharide (LPS, 1.5 mg/kg i.p.) or saline. Then, sexual partner preference was assessed at PND 60, 64, and 68, in a three-compartment chamber with a sexually receptive female and a male as potential partners simultaneously. The results confirmed that a single injection of LPS during puberty induced sickness signs indicative of an immune challenge. However, juvenile play was not affected by LPS treatment during the following days (PND36-40), nor was sexual behavior and partner preference for females in adulthood. These findings highlight that, while other studies have shown that LPS-induced immunological stress during puberty affects behavior and neuroendocrine responses, it does not affect juvenile play and sexual behavior in male rats. This suggests a remarkable resilience of these behavioral systems for adaptation to stressful experiences mediated by immune challenges during critical periods of development. These behaviors, however, might be affected by other types of stress.


Sujet(s)
Lipopolysaccharides , Maturation sexuelle , Stress psychologique , Animaux , Mâle , Lipopolysaccharides/pharmacologie , Femelle , Stress psychologique/physiopathologie , Rats , Maturation sexuelle/physiologie , Jeu et accessoires de jeu/psychologie , Comportement sexuel chez les animaux/physiologie , Comportement sexuel chez les animaux/effets des médicaments et des substances chimiques , Rat Wistar , Facteurs âges , Animaux nouveau-nés , Préférence d'accouplement chez les animaux/effets des médicaments et des substances chimiques , Préférence d'accouplement chez les animaux/physiologie
14.
Protein Sci ; 33(8): e5091, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38980078

RÉSUMÉ

Protein misfolding and aggregation are involved in several neurodegenerative disorders, such as α-synuclein (αSyn) implicated in Parkinson's disease, where new therapeutic approaches remain essential to combat these devastating diseases. Elucidating the microscopic nucleation mechanisms has opened new opportunities to develop therapeutics against toxic mechanisms and species. Here, we show that naturally occurring molecular chaperones, represented by the anti-amyloid Bri2 BRICHOS domain, can be used to target αSyn-associated nucleation processes and structural species related to neurotoxicity. Our findings revealed that BRICHOS predominantly suppresses the formation of new nucleation units on the fibrils surface (secondary nucleation), decreasing the oligomer generation rate. Further, BRICHOS directly binds to oligomeric αSyn species and effectively diminishes αSyn fibril-related toxicity. Hence, our studies show that molecular chaperones can be utilized as tools to target molecular processes and structural species related to αSyn neurotoxicity and have the potential as protein-based treatments against neurodegenerative disorders.


Sujet(s)
Chaperons moléculaires , alpha-Synucléine , alpha-Synucléine/composition chimique , alpha-Synucléine/métabolisme , alpha-Synucléine/toxicité , Humains , Chaperons moléculaires/composition chimique , Chaperons moléculaires/métabolisme , Protéines adaptatrices de la transduction du signal/composition chimique , Protéines adaptatrices de la transduction du signal/métabolisme , Domaines protéiques
15.
Chembiochem ; : e202400401, 2024 Jul 09.
Article de Anglais | MEDLINE | ID: mdl-38981854

RÉSUMÉ

A molecular switch based on the metastable radical anion derived from a substituted heteroaryl quinone is described. Pyrrolyl quinone thiocyanate (PQ 9) showed an interaction with the fluoride anion that was visible to the naked eye and quantified by UV/vis and 1H and 13 C NMR. The metastable quinoid species formed by the interaction with F- ("ON" state) showed a molecular switching effect autocontrolled by the presence of ascorbate ("OFF" state) and back to the "ON" state by an autooxidation process, measured by visible and UV/vis spectroscopy. Due to its out-of-equilibrium properties and the exchange of matter and energy, a dissipative structural behaviour is proposed. Considering its similarity to the mechanism of coenzyme Q in oxidative phosphophorylation, PQ 9 was evaluated on Saccharomyces cerevisiae mitochondrial function for inhibition of complexes II, III and IV, reactive oxygen species (ROS) production, catalase activity and lipid peroxidation. The results showed that PQ 9 inhibited complex III activity as well as the activity of all electron transport chain (ETC) complexes. In addition, PQ 9 reduced ROS production and catalase activity in yeast. The results suggest that PQ 9 may have potential applications as a new microbicidal compound by inducing ETC dysfunction.

16.
Front Cell Neurosci ; 18: 1398862, 2024.
Article de Anglais | MEDLINE | ID: mdl-38988663

RÉSUMÉ

The histochemical Falck-Hillarp method for the localization of dopamine (DA), noradrenaline (NA) and serotonin in the central nervous system (CNS) of rodents was introduced in the 1960s. It supported the existence of chemical neurotransmission in the CNS. The monoamine neurons in the lower brain stem formed monosynaptic ascending systems to the telencephalon and diencephalon and monoamine descending systems to the entire spinal cord. The monoamines were early on suggested to operate via synaptic chemical transmission in the CNS. This chemical transmission reduced the impact of electrical transmission. In 1969 and the 1970s indications were obtained that important modes of chemical monoamine communication in the CNS also took place through the extra-synaptic fluid, the extracellular fluid, and long-distance communication in the cerebrospinal fluid involving diffusion and flow of transmitters like DA, NA and serotonin. In 1986, this type of transmission was named volume transmission (VT) by Agnati and Fuxe and their colleagues, also characterized by transmitter varicosity and receptor mismatches. The short and long-distance VT pathways were characterized by volume fraction, tortuosity and clearance. Electrical transmission also exists in the mammalian CNS, but chemical transmission is in dominance. One electrical mode is represented by electrical synapses formed by gap junctions which represent low resistant passages between nerve cells. It allows for a more rapid passage of action potentials between nerve cells compared to chemical transmission. The second mode is based on the ability of synaptic currents to generate electrical fields to modulate chemical transmission. One aim is to understand how chemical transmission can be integrated with electrical transmission and how putative (aquaporin water channel, dopamine D2R and adenosine A2AR) complexes in astrocytes can significancy participate in the clearance of waste products from the glymphatic system. VT may also help accomplish the operation of the acupuncture meridians essential for Chinese medicine in view of the indicated existence of extracellular VT pathways.

17.
Nutr Hosp ; 41(4): 775-780, 2024 Aug 29.
Article de Espagnol | MEDLINE | ID: mdl-38967288

RÉSUMÉ

Introduction: Introduction: overweight and obesity in children are serious public health problems in Mexico. Objective: to analyze the behavior of the prevalence of overweight and obesity in children from 5 to 11 years of age and to present projections on the prevalence for the period 2022-2026. Methodology: ecological and retrospective study whose units of analysis were groups of children of Mexico with overweight and obesity in the period 1999-2021, according to information collected from six National Health and Nutrition Surveys. For the projections the classical method of least squares was used, for a trend analysis of both conditions for the period 2022-2026. Results: overweight in girls and obesity in boys shows a high prevalence in the period 1999-2021, even though the trend analysis for the period 2022-2026 shows a slight decrease in overweight for the group of boys and a slight increase in overweight for girls, as well in obesity for both groups. Conclusions: due to the high prevalence of overweight and obesity in children from 5 to 11 years of age in Mexico, an interdisciplinary approach is required to identify which dimensions (biochemical, psychological, interpersonal and social) participate in the problem, considering three environments contributing for psychological and social development of children, the ecological-social, the family and the school.


Introducción: Introducción: el sobrepeso y la obesidad en niños son serios problemas de salud pública en México. Objetivo: analizar el comportamiento de la prevalencia de sobrepeso y obesidad en niños de 5 a 11 años y presentar proyecciones sobre su prevalencia para el periodo 2022-2026. Metodología: estudio ecológico y retrospectivo cuyas unidades de análisis fueron grupos de niños con sobrepeso y obesidad en el periodo 1999-2021, de acuerdo con información recabada en seis Encuestas Nacionales de Salud y Nutrición en México. Para las proyecciones se utilizó el método clásico de mínimos cuadrados, con el que se realizó un análisis de tendencia de ambas condiciones para el periodo 2022-2026. Resultados: el sobrepeso en niñas y la obesidad en niños muestra una elevada prevalencia en el periodo 1999-2021, aun cuando el análisis de tendencia para el periodo 2022-2026 muestra un ligero decremento en el sobrepeso para el grupo de niños y un ligero incremento en el sobrepeso para las niñas, así como en la obesidad para ambos grupos. Conclusión: Debido a la elevada prevalencia de sobrepeso y obesidad en niños de 5 a 11 años en México, se precisa de su abordaje interdisciplinario para identificar qué dimensiones (bioquímica, psicológica, interpersonal y social) participan en el problema, considerando tres ambientes que contribuyen al desarrollo psicológico y social de los niños, el ecológico-social, el familiar y el escolar.


Sujet(s)
Surpoids , Obésité pédiatrique , Humains , Mexique/épidémiologie , Mâle , Femelle , Enfant d'âge préscolaire , Surpoids/épidémiologie , Enfant , Études rétrospectives , Prévalence , Obésité pédiatrique/épidémiologie , Enquêtes nutritionnelles , Obésité/épidémiologie , Facteurs sexuels
18.
Ann Surg Open ; 5(2): e431, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38911621

RÉSUMÉ

Objective: To describe rates of dexamethasone use in the nonoperative management of malignant small bowel obstruction (mSBO) and their outcomes. Background: mSBO is common in patients with advanced abdominal-pelvic cancers. Management includes prioritizing quality of life and avoiding surgical intervention when possible. The use of dexamethasone to restore bowel function is recommended in the National Comprehensive Cancer Network guidelines for mSBO. Yet, it is unknown how often dexamethasone is used for mSBO and whether results from nonresearch settings support its use. Methods: This is a multicenter retrospective cohort study including unique admissions for mSBO from January 1, 2019 to December 31, 2021. Dexamethasone use and management outcomes were summarized with descriptive statistics and multiple logistic regression. Results: Among 571 admissions (68% female, mean age 63 years, 85% history of abdominal surgery) that were eligible and initially nonoperative, 26% [95% confidence interval (CI) = 23%-30%] received dexamethasone treatment (69% female, mean age 62 years, 87% history of abdominal surgery). Dexamethasone use by site ranged from 13% to 52%. Among dexamethasone recipients, 13% (95% CI = 9%-20%) subsequently required nonelective surgery during the same admission and 4 dexamethasone-related safety-events were reported. Amongst 421 eligible admissions where dexamethasone was not used, 17% (95% CI = 14%-21%) required nonelective surgery. Overall, the unadjusted odds ratio (OR) for nonelective surgery with dexamethasone use compared to without its use was 0.7 (95% CI = 0.4-1.3). Using multiple logistic regression, OR after adjusting for site, age, sex, history of abdominal surgery, nasogastric tube, and Gastrografin use was 0.6 (95% CI = 0.3-1.1). Conclusion: Dexamethasone was used in about 1 in 4 eligible mSBO admissions with high variability of use between tertiary academic centers. This multicenter retrospective cohort study suggested an association between dexamethasone use and lower rates of nonelective surgery, representing a potential opportunity for quality improvement.

19.
Microorganisms ; 12(6)2024 May 24.
Article de Anglais | MEDLINE | ID: mdl-38930447

RÉSUMÉ

Chagas Disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, affecting 6-8 million people, mainly in Latin America. The medical treatment is based on two compounds, benznidazole and nifurtimox, with limited effectiveness and that produce severe side effects; consequently, there is an urgent need to develop new, safe, and effective drugs. Amphotericin B is the most potent antimycotic known to date. A21 is a derivative of this compound with the property of binding to ergosterol present in cell membranes of some organisms. In the search for a new therapeutic drug against T. cruzi, the objective of this work was to study the in vitro and in vivo effects of A21 derivative on T. cruzi. Our results show that the A21 increased the reactive oxygen species and reduced the mitochondrial membrane potential, affecting the morphology, metabolism, and cell membrane permeability of T. cruzi in vitro. Even more important was finding that in an in vivo murine model of infection, A21 in combination with benznidazole was able to reduce blood parasitemia, diminish the immune inflammatory infiltrate in skeletal muscle and rescue all the mice from death due to a virulent T. cruzi strain.

20.
Plant Phenomics ; 6: 0202, 2024.
Article de Anglais | MEDLINE | ID: mdl-38939746

RÉSUMÉ

Grape cluster architecture and compactness are complex traits influencing disease susceptibility, fruit quality, and yield. Evaluation methods for these traits include visual scoring, manual methodologies, and computer vision, with the latter being the most scalable approach. Most of the existing computer vision approaches for processing cluster images often rely on conventional segmentation or machine learning with extensive training and limited generalization. The Segment Anything Model (SAM), a novel foundation model trained on a massive image dataset, enables automated object segmentation without additional training. This study demonstrates out-of-the-box SAM's high accuracy in identifying individual berries in 2-dimensional (2D) cluster images. Using this model, we managed to segment approximately 3,500 cluster images, generating over 150,000 berry masks, each linked with spatial coordinates within their clusters. The correlation between human-identified berries and SAM predictions was very strong (Pearson's r2 = 0.96). Although the visible berry count in images typically underestimates the actual cluster berry count due to visibility issues, we demonstrated that this discrepancy could be adjusted using a linear regression model (adjusted R 2 = 0.87). We emphasized the critical importance of the angle at which the cluster is imaged, noting its substantial effect on berry counts and architecture. We proposed different approaches in which berry location information facilitated the calculation of complex features related to cluster architecture and compactness. Finally, we discussed SAM's potential integration into currently available pipelines for image generation and processing in vineyard conditions.

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