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1.
Cell ; 177(6): 1583-1599.e16, 2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-31150624

RESUMO

T and B cells are the two known lineages of adaptive immune cells. Here, we describe a previously unknown lymphocyte that is a dual expresser (DE) of TCR and BCR and key lineage markers of both B and T cells. In type 1 diabetes (T1D), DEs are predominated by one clonotype that encodes a potent CD4 T cell autoantigen in its antigen binding site. Molecular dynamics simulations revealed that this peptide has an optimal binding register for diabetogenic HLA-DQ8. In concordance, a synthetic version of the peptide forms stable DQ8 complexes and potently stimulates autoreactive CD4 T cells from T1D patients, but not healthy controls. Moreover, mAbs bearing this clonotype are autoreactive against CD4 T cells and inhibit insulin tetramer binding to CD4 T cells. Thus, compartmentalization of adaptive immune cells into T and B cells is not absolute, and violators of this paradigm are likely key drivers of autoimmune diseases.


Assuntos
Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Diabetes Mellitus Tipo 1/imunologia , Adolescente , Adulto , Autoantígenos/imunologia , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/metabolismo , Epitopos/imunologia , Feminino , Células HEK293 , Antígenos HLA-DQ/imunologia , Antígenos HLA-DQ/ultraestrutura , Humanos , Ativação Linfocitária/imunologia , Linfócitos/imunologia , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Simulação de Dinâmica Molecular , Peptídeos , Ligação Proteica/imunologia
2.
J Virol ; 98(4): e0014624, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38440983

RESUMO

Peste des petits ruminants is an acute and highly contagious disease caused by the Peste des petits ruminants virus (PPRV). Host proteins play a crucial role in viral replication. However, the effect of fusion (F) protein-interacting partners on PPRV infection is poorly understood. In this study, we found that the expression of goat plasminogen activator urokinase (PLAU) gradually decreased in a time- and dose-dependent manner in PPRV-infected goat alveolar macrophages (GAMs). Goat PLAU was subsequently identified using co-immunoprecipitation and confocal microscopy as an F protein binding partner. The overexpression of goat PLAU inhibited PPRV growth and replication, whereas silencing goat PLAU promoted viral growth and replication. Additionally, we confirmed that goat PLAU interacted with a virus-induced signaling adapter (VISA) to antagonize F-mediated VISA degradation, increasing the production of type I interferon. We also found that goat PLAU reduced the inhibition of PPRV replication in VISA-knockdown GAMs. Our results show that the host protein PLAU inhibits the growth and replication of PPRV by VISA-triggering RIG-I-like receptors and provides insight into the host protein that antagonizes PPRV immunosuppression.IMPORTANCEThe role of host proteins that interact with Peste des petits ruminants virus (PPRV) fusion (F) protein in PPRV replication is poorly understood. This study confirmed that goat plasminogen activator urokinase (PLAU) interacts with the PPRV F protein. We further discovered that goat PLAU inhibited PPRV replication by enhancing virus-induced signaling adapter (VISA) expression and reducing the ability of the F protein to degrade VISA. These findings offer insights into host resistance to viral invasion and suggest new strategies and directions for developing PPR vaccines.


Assuntos
Doenças das Cabras , Cabras , Interações Hospedeiro-Patógeno , Peste dos Pequenos Ruminantes , Vírus da Peste dos Pequenos Ruminantes , Ativador de Plasminogênio Tipo Uroquinase , Proteínas Virais de Fusão , Animais , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteína DEAD-box 58/metabolismo , Doenças das Cabras/imunologia , Doenças das Cabras/metabolismo , Doenças das Cabras/virologia , Cabras/imunologia , Cabras/virologia , Macrófagos Alveolares , Peste dos Pequenos Ruminantes/imunologia , Peste dos Pequenos Ruminantes/metabolismo , Peste dos Pequenos Ruminantes/virologia , Vírus da Peste dos Pequenos Ruminantes/crescimento & desenvolvimento , Vírus da Peste dos Pequenos Ruminantes/imunologia , Vírus da Peste dos Pequenos Ruminantes/metabolismo , Ligação Proteica , Ativador de Plasminogênio Tipo Uroquinase/genética , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Proteínas Virais de Fusão/metabolismo
3.
Catheter Cardiovasc Interv ; 104(1): 92-96, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38686525

RESUMO

The double-kiss mini-crush (DKMC) technique has been successfully deployed in the past for the treatment of complex coronary lesions even for left main lesions. Our case report consists of a proof-of-principle that the DKMC technique can be successfully translated as well to the field of complex renal artery lesions. Insightful thinking out-of-the "coronary" box in concert with skillful off-label application of coronary stenting procedures may open the gate for unprecedented opportunities for the treatment of difficult-to-tackle in-stent restenosis in the renal circulation.


Assuntos
Recidiva , Obstrução da Artéria Renal , Stents , Humanos , Obstrução da Artéria Renal/diagnóstico por imagem , Obstrução da Artéria Renal/terapia , Obstrução da Artéria Renal/fisiopatologia , Obstrução da Artéria Renal/etiologia , Resultado do Tratamento , Masculino , Angioplastia com Balão/instrumentação , Grau de Desobstrução Vascular , Idoso , Artéria Renal/diagnóstico por imagem , Artéria Renal/fisiopatologia
4.
Inflamm Res ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965133

RESUMO

OBJECTIVE: We aimed to broaden our understanding of a potential interaction between B1R and TLR4, considering earlier studies suggesting that lipopolysaccharide (LPS) may trigger B1R stimulation. METHODS: We assessed the impact of DBK and LPS on the membrane potential of thoracic aortas from C57BL/6, B1R, or TLR4 knockout mice. Additionally, we examined the staining patterns of these receptors in the thoracic aortas of C57BL/6 and in endothelial cells (HBMEC). RESULTS: DBK does not affect the resting membrane potential of aortic rings in C57BL/6 mice, but it hyperpolarizes preparations in B1KO and TLR4KO mice. The hyperpolarization mechanism in B1KO mice involves B2R, and the TLR4KO response is independent of cytoplasmic calcium influx but relies on potassium channels. Conversely, LPS hyperpolarizes thoracic aorta rings in both C57BL/6 and B1KO mice, with the response unaffected by a B1R antagonist. Interestingly, the absence of B1R alters the LPS response to potassium channels. These activities are independent of nitric oxide synthase (NOS). While exposure to DBK and LPS does not alter B1R and TLR4 mRNA expression, treatment with these agonists increases B1R staining in endothelial cells of thoracic aortic rings and modifies the staining pattern of B1R and TLR4 in endothelial cells. Proximity ligation assay suggests a interaction between the receptors. CONCLUSION: Our findings provide additional support for a putative connection between B1R and TLR4 signaling. Given the involvement of these receptors and their agonists in inflammation, it suggests that drugs and therapies targeting their effects could be promising therapeutic avenues worth exploring.

5.
Circ J ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38987207

RESUMO

BACKGROUND: Coronary angioscopy (CAS) has 2 unique abilities: direct visualization of thrombi and plaque color. However, in the recent drug-eluting stent (DES) era, serial CAS findings after DES implantation have not been fully elucidated. We investigated the impact of CAS findings after implantation of a polymer-free biolimus A9-coated stent (PF-BCS) or durable polymer everolimus-eluting stent (DP-EES).Methods and Results: We investigated serial CAS and optical coherence tomography (OCT) findings at 1 and 12 months in 99 patients who underwent PF-BCS or DP-EES implantation. We evaluated factors correlated with angioscopic thrombi and yellow plaque, and the clinical impact of both thrombi and yellow plaque at 12 months (BTY). The BTY group included 17 (22%) patients. The incidence and grade of thrombi and yellow plaque decreased from 1 to 12 months. Although no patients had newly appearing thrombi at 12 months, 2 DP-EES patients had newly appearing yellow plaque at 12 months. Multivariable analysis revealed HbA1c, minimum stent area, and adequate strut coverage were significant factors correlated with 12-month angioscopic thrombi, and DP-EESs were significantly correlated with 12-month yellow plaque. However, BTY was not correlated with clinical events. CONCLUSIONS: The management of diabetes, stent area, and adequate stent coverage are important for intrastent thrombogenicity and polymer-free stents are useful for stabilizing plaque vulnerability.

6.
Macromol Rapid Commun ; : e2400405, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007171

RESUMO

Over the past two decades, deep eutectic solvents (DESs) have captured significant attention as an emergent class of solvents that have unique properties and applications in differing fields of chemistry. One area where DES systems find utility is the design of polymeric gels, often referred to as "eutectogels," which can be prepared either using a DES to replace a traditional solvent, or where monomers form part of the DES themselves. Due to the extensive network of intramolecular interactions (e.g., hydrogen bonding) and ionic species that exist in DES systems, polymeric eutectogels often possess appealing material properties-high adhesive strength, tuneable viscosity, rapid polymerization kinetics, good conductivity, as well as high strength and flexibility. In addition, non-covalent crosslinking approaches are possible due to the inherent interactions that exist in these materials. This review considers several key applications of polymeric eutectogels, including organic electronics, wearable sensor technologies, 3D printing resins, adhesives, and a range of various biomedical applications. The design, synthesis, and properties of these eutectogels are discussed, in addition to the advantages of this synthetic approach in comparison to traditional gel design. Perspectives on the future directions of this field are also highlighted.

7.
Bioorg Chem ; 145: 107233, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38422591

RESUMO

Dihydroceramide desaturase 1 (Des1) catalyzes the formation of a CC double bond in dihydroceramide to furnish ceramide. Inhibition of Des1 is related to cell cycle arrest and programmed cell death. The lack of the Des1 crystalline structure, as well as that of a close homologue, hampers the detailed understanding of its inhibition mechanism and difficults the design of new inhibitors, thus making Des1 a strategic target. Based on previous structure-activity studies, different ceramides containing rigid scaffolds were designed. The synthesis and evaluation of these compounds as Des1 inhibitors allowed the identification of PR280 as a better Des 1 inhibitor in vitro (IC50 = 700 nM) than GT11 and XM462, the current reference inhibitors. This cyclopropenone ceramide was obtained in a 6-step synthesis with a 24 % overall yield. The highly confident 3D structure of Des1, recently predicted by AlphaFold2, served as the basis for conducting docking studies of known Des1 inhibitors and the ceramide derivatives synthesized by us in this study. For this purpose, a complete holoprotein structure was previously constructed. This study has allowed a better knowledge of key ligand-enzyme interactions for Des1 inhibitory activity. Furthermore, it sheds some light on the inhibition mechanism of GT11.


Assuntos
Ceramidas , Oxirredutases , Ceramidas/farmacologia , Ceramidas/química , Oxirredutases/metabolismo , Ciclopropanos/farmacologia
8.
Gen Comp Endocrinol ; 351: 114475, 2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38382621

RESUMO

Several metabolic hormones signal an organism's energy balance to the brain and modulate feeding behaviours accordingly. These metabolic signals may also regulate other behaviour related to energy balance, such as food caching or hoarding. Ghrelin is one such hormone, but it appears to exert different effects on appetite and fat levels in birds and mammals. Ghrelin treatment inhibits food intake and decreases fat stores in some bird species, but these effects may differ between acylated and unacylated (des-acyl) forms of ghrelin. The effect of ghrelin on food caching in birds has been examined in only one study, that found both leptin and unacylated ghrelin reduced food caching and mass gain in coal tits (Periparus ater). We expanded on this to test how both forms of ghrelin affect food caching and body composition in black-capped chickadees (Poecile atricapillus). We injected each bird with acylated ghrelin, unacylated ghrelin, and a saline control and then measured food caching every 20 min for two hours post-injection. We also measured body mass fat levels the day before, and after treatment using quantitative magnetic resonance (QMR). Contrary to prior work, we found no effects of either form of ghrelin on food caching, or body or fat mass. Future work is required to determine if the difference between our results and those of the prior study stems from species differences in response to ghrelin and/or in the motivation to cache food, or ghrelin effects being modulated by energy reserves.


Assuntos
Grelina , Aves Canoras , Animais , Grelina/farmacologia , Aves Canoras/fisiologia , Comportamento Alimentar/fisiologia , Alimentos , Composição Corporal , Mamíferos
9.
Can J Psychiatry ; 69(7): 524-535, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38571478

RESUMO

OBJECTIVES: Cannabis use is common in people with early-phase psychosis (EP) and is associated with worse treatment outcomes. Few targeted interventions for cannabis use behaviour in this population exist, most focusing on abstinence, none focusing on harm reduction. Many people with EP will not seek treatment for their cannabis use with current therapeutic options. Understanding preferences for cannabis-focused harm reduction interventions may be key to improving outcomes. This study aimed to determine preferences of young adults with EP who use cannabis for cannabis-focused harm reduction interventions. METHODS: Eighty-nine young adults across Canada with EP interested in reducing cannabis-related harms were recruited. An online questionnaire combining conventional survey methodology and two unique discrete choice experiments (DCEs) was administered. One DCE focused on attributes of core harm reduction interventions (DCE 1) and the second on attributes of boosters (DCE 2). We analysed these using mixed ranked-ordered logistic regression models. Preference questions using conventional survey methodology were analysed using summary statistics. RESULTS: Preferred characteristics for cannabis-focused harm reduction interventions (DCE 1) were: shorter sessions (60 min vs. 10 min, odds ratio (OR): 0.72; P < 0.001); less frequent sessions (daily vs. monthly, OR: 0.68; P < 0.001); shorter interventions (3 months vs. 1 month, OR: 0.80; P < 0.01); technology-based interventions (vs. in-person, OR: 1.17; P < 0.05). Preferences for post-intervention boosters (DCE 2) included opting into boosters (vs. opting out, OR: 3.53; P < 0.001) and having shorter boosters (3 months vs. 1 month, OR: 0.79; P < 0.01). Nearly half of the participants preferred to reduce cannabis use as a principal intervention goal (vs. using in less harmful ways or avoiding risky situations). CONCLUSIONS: Further research is required to see if technology-based harm reduction interventions for cannabis featuring these preferences translate into greater engagement and improved outcomes in EP patients.


Assuntos
Redução do Dano , Preferência do Paciente , Transtornos Psicóticos , Humanos , Masculino , Feminino , Adulto Jovem , Estudos Transversais , Adulto , Transtornos Psicóticos/terapia , Canadá , Adolescente , Uso da Maconha
10.
Can J Psychiatry ; 69(5): 358-368, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38174363

RESUMO

OBJECTIVE: Responsible media reporting is an accepted strategy for preventing suicide. In 2015, suicide prevention experts launched a media engagement initiative aimed at improving suicide-related reporting in Canada; its impact on media reporting quality and suicide deaths is unknown. METHOD: This pre-post observational study examined changes in reporting characteristics in a random sample of suicide-related articles from major publications in the Greater Toronto Area (GTA) media market. Articles (n = 900) included 450 from the 6-year periods prior to and after the initiative began. We also examined changes in suicide counts in the GTA between these epochs. We used chi-square tests to analyse changes in reporting characteristics and time-series analyses to identify changes in suicide counts. Secondary outcomes focused on guidelines developed by media professionals in Canada and how they may have influenced media reporting quality as well as on the overarching narrative of media articles during the most recent years of available data. RESULTS: Across-the-board improvement was observed in suicide-related reporting with substantial reductions in many elements of putatively harmful content and substantial increases in all aspects of putatively protective content. However, overarching article narratives remained potentially harmful with 55.2% of articles telling the story of someone's death and 20.8% presenting an other negative message. Only 3.6% of articles told a story of survival. After controlling for potential confounders, a nonsignificant numeric decrease in suicide counts was identified after initiative implementation (ω = -5.41, SE = 3.43, t = 1.58, p = 0.12). CONCLUSIONS: We found evidence that a strategy to engage media in Canada changed the content of reporting, but there was only a nonsignificant trend towards fewer suicides. A more fundamental change in media narratives to focus on survival rather than death appears warranted.


Assuntos
Suicídio , Humanos , Canadá , Projetos de Pesquisa , Prevenção do Suicídio
11.
Can J Psychiatry ; : 7067437241255096, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747934

RESUMO

OBJECTIVES: The aetiology of mental disorders involves genetic and environmental factors, both reflected in family health history. We examined the intergenerational transmission of multiple mental disorders from parents and grandparents using population-based, objectively measured family histories. METHODS: This population-based retrospective cohort study used administrative healthcare databases in Manitoba, Canada and included adults living in Manitoba from 1977 to 2020 with linkages to at least one parent and one grandparent. Index date was when individuals turned 18 or 1 April 1977, whichever occurred later. Mental disorder diagnoses (mood and anxiety, substance use and psychotic disorders) were identified in individuals, parents and grandparents from hospitalization and outpatient records. Cox proportional hazards regression models included sociodemographic characteristics, individual's comorbidity and mental disorder history in a grandparent, mother and father. RESULTS: Of 109,359 individuals with no mental disorder prior to index date, 47.1% were female, 36.3% had a mental disorder during follow-up, and 90.9% had a parent or grandparent with a history of a mental disorder prior to the index date. Both paternal and maternal history of a mental disorder increased the risk of the disorder in individuals. Psychotic disorders had the strongest association with parental history and were mostly influenced by paternal (hazards ratio [HR] 3.73, 95% confidence interval [CI] 2.99 to 4.64) compared to maternal history (HR 2.23, 95% CI, 1.89 to 2.64). Grandparent history was independently associated with the risk of all mental disorders but had the strongest influence on substance use disorders (HR 1.42, 95% CI, 1.34 to 1.50). CONCLUSIONS: Parental history of mental disorders was associated with an increased risk of all mental disorders. Grandparent history of mental disorders was associated with a small risk increase of the disorders above and beyond parental history influence. This three-generation study further highlights the need for family-based interventional programs in families affected by mental disorders. PLAIN LANGUAGE SUMMARY TITLE: The Intergenerational Transfer of Mental Illnesses.


ObjectivesBoth genetics and environmental factors, such as poverty, maltreatment and parental education, have a role in the development of mental illnesses. Some genetic and environmental risk factors for mental illnesses are shared within families. We conducted a large study to test the extent to which mental illnesses are passed down through generations.MethodsThis study used healthcare data from Manitoba, Canada captured during the delivery of healthcare services for administrative purposes. These data included all adults from 1977 to 2020 who had at least one parent and one grandparent with linked data. Mental illnesses were diagnosed in individuals, parents and grandparents by doctors during hospitalizations or physician visits. The illnesses included mood and anxiety, substance use, and psychotic illnesses. We estimated the likelihood of developing a mental illness when parents and/or grandparents had a mental illness as well.ResultsThe study included 109,359 individuals; a third developed a mental illness during the study period. The majority had a history of a mental illness in a parent or grandparent. We found that a history of mental illness in a mother and father increased the chance of developing the illness. Psychotic illnesses had the strongest relation with parental history. In particular, having a father with a psychotic illness increased the chance of developing the illness by four times. The likelihood of developing a mental illness was higher if a grandparent had a mental illness, above and beyond parental history influence, particularly for substance use disorders.ConclusionsHaving a parent or grandparent with a mental illness increases an individual's chance of developing a mental illness. Family-based intervention programs are needed to support families affected by mental illnesses in coping with their heavy burden.

12.
Can J Psychiatry ; 69(7): 513-523, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38425284

RESUMO

OBJECTIVES: To characterize the effects of adjunctive brexpiprazole on patient life engagement and depressive symptoms in patients with major depressive disorder (MDD) using patient-reported outcomes. METHODS: An 8-week, Phase 4, open-label, interventional study was conducted at 15 Canadian trial sites between April 2021 and May 2022. Adult outpatients with MDD (at least moderately severe) and inadequate response to 1-2 antidepressants continued their current antidepressant and received oral adjunctive brexpiprazole 0.5-2 mg/day. Co-primary endpoints were change from baseline to Week 8 in Inventory of Depressive Symptomatology Self-Report (IDS-SR) 10-item Life Engagement subscale score, and IDS-SR 30-item total score. Safety was assessed by standard variables. RESULTS: Of 122 enrolled patients, 120 (98.4%) were treated (mean [SD] dose: 1.2 [0.4] mg/day) and analyzed, and 111 (91.0%) completed the study. Statistically significant least squares mean improvements to Week 8 were observed on IDS-SR10 Life Engagement subscale score (baseline mean [SD]: 16.1 [4.7]; change [95% confidence interval]: -8.11 [-9.34, -6.88]; p < 0.001) and IDS-SR total score (baseline mean [SD]: 41.3 [9.8]; change [95% confidence interval]: -17.38 [-20.08, -14.68]; p < 0.001). Improvements were observed from Week 2, onwards. Treatment-emergent adverse events with incidence ≥5% were fatigue (n = 13, 10.8%), headache (n = 13, 10.8%), insomnia (n = 12, 10.0%), nausea (n = 9, 7.5%), tremor (n = 8, 6.7%), and weight increase (n = 7, 5.8%). Six patients (5.0%) discontinued due to adverse events. Mean (SD) change in body weight from baseline to last visit was +1.9 (3.4) kg. CONCLUSIONS: Using an exploratory patient-reported outcome measure, patients with MDD and inadequate response to antidepressants who received open-label adjunctive brexpiprazole showed early and clinically meaningful improvement in patient life engagement, which should be further assessed in a prospective randomized controlled trial. Patient-rated depressive symptoms (on the validated 30-item IDS-SR) also improved. Adjunctive brexpiprazole was well tolerated, and no new safety signals were observed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04830215.


Assuntos
Antidepressivos , Transtorno Depressivo Maior , Medidas de Resultados Relatados pelo Paciente , Quinolonas , Tiofenos , Humanos , Masculino , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Adulto , Pessoa de Meia-Idade , Canadá , Antidepressivos/efeitos adversos , Antidepressivos/administração & dosagem , Quinolonas/efeitos adversos , Quinolonas/administração & dosagem , Quinolonas/farmacologia , Tiofenos/efeitos adversos , Tiofenos/administração & dosagem , Tiofenos/farmacologia , Quimioterapia Combinada
13.
Neurosurg Focus ; 56(3): E11, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38428002

RESUMO

OBJECTIVE: Endovascular and microsurgical treatment are viable options for the majority of Borden type III dural arteriovenous fistulas (dAVFs). The aim of this study was to examine treatment outcomes in a comparative analysis of endovascular and surgical treatment modalities for Borden type III fistulas and explore clinical implications of the DES scheme in selecting ideal candidates for surgical therapy. METHODS: Patients diagnosed with dAVFs with leptomeningeal venous drainage admitted to the Departments of Neurosurgery or Neuroradiology of the University Hospital Zurich between January 2014 and October 2021 were included in this study. Comprehensive patient data including demographics, clinical presentation, and dAVF characteristics, including established classifications, were collected. Treatment outcomes were assessed based on postinterventional angiography findings. In addition, treatment-related complications were assessed based on the Clavien-Dindo classification. RESULTS: Among all Borden type III dAVFs, 15 were initially treated endovascularly (60% complete occlusion rate) and 10 with microsurgical disconnection (90% complete occlusion rate) (p = 0.18). Subgroup analysis of dAVFs meeting the criteria for directness and exclusivity based on the DES scheme showed a 100% complete occlusion rate after microsurgical disconnection, whereas embolization achieved a complete occlusion rate of 60% (p = 0.06). There was no significant difference in the rate or severity of treatment-related complications between treatment modalities. CONCLUSIONS: This study suggests that microsurgical disconnection is a viable primary treatment modality for Borden type III dAVFs, particularly for dAVFs that meet the criteria of directness and exclusivity according to the DES scheme. The DES scheme demonstrates its relevance in selecting the most appropriate treatment strategy for affected patients.


Assuntos
Malformações Vasculares do Sistema Nervoso Central , Embolização Terapêutica , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Angiografia , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/cirurgia
14.
Int J Mol Sci ; 25(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38892455

RESUMO

Arrhythmogenic cardiomyopathy (ACM) is an inherited myocardial disease at risk of sudden death. Genetic testing impacts greatly in ACM diagnosis, but gene-disease associations have yet to be determined for the increasing number of genes included in clinical panels. Genetic variants evaluation was undertaken for the most relevant non-desmosomal disease genes. We retrospectively studied 320 unrelated Italian ACM patients, including 243 cases with predominant right-ventricular (ARVC) and 77 cases with predominant left-ventricular (ALVC) involvement, who did not carry pathogenic/likely pathogenic (P/LP) variants in desmosome-coding genes. The aim was to assess rare genetic variants in transmembrane protein 43 (TMEM43), desmin (DES), phospholamban (PLN), filamin c (FLNC), cadherin 2 (CDH2), and tight junction protein 1 (TJP1), based on current adjudication guidelines and reappraisal on reported literature data. Thirty-five rare genetic variants, including 23 (64%) P/LP, were identified in 39 patients (16/243 ARVC; 23/77 ALVC): 22 FLNC, 9 DES, 2 TMEM43, and 2 CDH2. No P/LP variants were found in PLN and TJP1 genes. Gene-based burden analysis, including P/LP variants reported in literature, showed significant enrichment for TMEM43 (3.79-fold), DES (10.31-fold), PLN (117.8-fold) and FLNC (107-fold). A non-desmosomal rare genetic variant is found in a minority of ARVC patients but in about one third of ALVC patients; as such, clinical decision-making should be driven by genes with robust evidence. More than two thirds of non-desmosomal P/LP variants occur in FLNC.


Assuntos
Displasia Arritmogênica Ventricular Direita , Humanos , Displasia Arritmogênica Ventricular Direita/genética , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Proteínas de Membrana/genética , Caderinas/genética , Desmossomos/genética , Desmossomos/metabolismo , Predisposição Genética para Doença , Variação Genética , Filaminas/genética , Estudos Retrospectivos , Itália , Proteínas de Ligação ao Cálcio/genética , Antígenos CD/genética
15.
Int J Mol Sci ; 25(4)2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38397016

RESUMO

The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the coagulation system is not fully understood. SARS-CoV-2 penetrates cells through angiotensin-converting enzyme 2 (ACE2) receptors, leading to its downregulation. Des-arginine9-bradykinin (DA9B) is degraded by ACE2 and causes vasodilation and increased vascular permeability. Furthermore, DA9B is associated with impaired platelet function. Therefore, the aim of this study was to evaluate the effects of DA9B on platelet function and coagulopathy in critically ill coronavirus disease 2019 (COVID-19) patients. In total, 29 polymerase-positive SARS-CoV-2 patients admitted to the intensive care unit of the University Hospital of Giessen and 29 healthy controls were included. Blood samples were taken, and platelet impedance aggregometry and rotational thromboelastometry were performed. Enzyme-linked immunosorbent assays measured the concentrations of DA9B, bradykinin, and angiotensin 2. Significantly increased concentrations of DA9B and angiotensin 2 were found in the COVID-19 patients. A negative effect of DA9B on platelet function and intrinsic coagulation was also found. A sub-analysis of moderate and severe acute respiratory distress syndrome patients revealed a negative association between DA9B and platelet counts and fibrinogen levels. DA9B provokes inhibitory effects on the intrinsic coagulation system in COVID-19 patients. This negative feedback seems reasonable as bradykinin, which is transformed to DA9B, is released after contact activation. Nevertheless, further studies are needed to confirm our findings.


Assuntos
COVID-19 , Humanos , SARS-CoV-2/metabolismo , Bradicinina/farmacologia , Bradicinina/metabolismo , Enzima de Conversão de Angiotensina 2 , Estado Terminal , Angiotensinas
16.
J Environ Manage ; 366: 121594, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38971061

RESUMO

In the management of urban drainage networks, great interest has been generated in the removal of sediments from sewer systems. The unsteady three-dimensional (3D) flow and turbulent coherent structures surrounding sediment reduction plates in a sewer system are investigated by means of the detached-eddy simulation (DES). Particular emphasis is given to detailing the instantaneous velocity and vorticity fields within the grooves, along with an examination of the three-dimensional, long-term, average flow structure at a Reynolds number of approximately 105. Velocity vectors demonstrate continuous flapping of the flow on the groove wall, periodically interacting with ejections of positive and negative vorticity originating from the grooves. The interaction between the three-dimensional groove flow and the shear flow leads to the downstream transport of patches of positive and negative vorticity, which significantly influence sediment transport. The high-velocity shear flows and strong vortices generated in undulating topography, as identified by the Q-criteria, are the key factors contributing to the efficient sediment reduction capabilities of the sediment reduction plates. The sediment reduction plates with partially enclosed structures exhibit low sedimentation rates in grooves on the plate, a broader acceleration region, and a lesser impact on the flow capacity. The results improve the understanding of the hydrodynamics and turbulent coherent structures surrounding the sediment reduction plates while elucidating the driving factors behind the enhancement of sediment scouring and suspension capacities. These results indicate that the redesign of the plates as partially enclosed structures contributes to further improving their sediment reduction performance.

17.
Can J Diet Pract Res ; : 1-8, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38634640

RESUMO

Literature on dietary behaviours of the pediatric Crohn's Disease (CD) population and the relationship between dietary intake and CD activity is limited. Three dietary indices were developed and tested to conduct dietary pattern analysis in pediatric patients with CD consuming a free diet following remission induction via exclusive enteral nutrition (n = 11). Index scores underwent descriptive and inferential analysis. The mean adjusted scores (out of 100) for the Pediatric Western Diet Index, Pediatric Prudent Diet Index, and Pediatric-Adapted 2010 Alternate Healthy Eating Index (PA2010-AHEI) were 29.82 ± 15.22, 34.25 ± 15.18, and 51.50 ± 11.69, respectively. The mean Western-to-Prudent ratio was 0.94 ± 0.55. A significant correlation (r = -0.71) and relationship (F[1, 9] = 9.04, P < 0.05, R2 = 0.501) between the Western-to-Prudent ratio and PA2010-AHEI was found. The results suggest participants were not following a Western or Prudent diet, and were consuming foods not captured by the indices. More research is needed to describe dietary intake of individuals with CD, validate dietary indices in diverse samples, and explore the utility of these indices in CD assessment and treatment. The co-authors hope this work will stimulate/inspire subsequent interprofessional, dietitian-led research on this topic.

18.
Can J Diet Pract Res ; 85(2): 59-65, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38465628

RESUMO

Purpose: This study aimed to assess the reliability and validity of an online approach to monitoring food affordability in Ontario using the updated Ontario Nutritious Food Basket (ONFB).Methods: The ONFB was priced online in 12 large multi-chain grocery stores to test intra-/inter-rater reliability using percent agreement and intra-class correlations (ICCs). Then, the ONFB was priced in-store and online in 28 stores to estimate food price differences using paired t-tests and Pearson's correlation for all (n =1708) and matched items (same product/brand and purchase unit) (n = 1134).Results: Intra-/inter-rater agreement was high (95.4%/81.6%; ICC = 0.972, F = 69.9, p < 0.001). On average, in-store prices were less than $0.02 lower than online prices. There were no significant differences between mean in-store and online prices for all items (t = 0.504 p = 0.614). The mean price was almost perfectly correlated between in-store and online (fully matched: R = 0.993 p < 0.001; all items: R = 0.967 p < 0.001). Online monthly ONFB estimates for a family of four were strongly correlated (R = 0.937 p < 0.001) with estimates calculated using in-store data.Conclusions: Online pricing is a reliable and valid approach to food costing in Ontario that contributes to modernizing the monitoring of food affordability in Canada and abroad.


Assuntos
Comércio , Internet , Ontário , Reprodutibilidade dos Testes , Humanos , Abastecimento de Alimentos/economia , Abastecimento de Alimentos/estatística & dados numéricos , Custos e Análise de Custo , Alimentos/economia , Valor Nutritivo
19.
Can J Diet Pract Res ; 85(2): 101-105, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38564450

RESUMO

Land2Lab is an evolving community-based intergenerational program that brings together Elders and youth on the land and in the kitchen and lab to share and celebrate Mi'kmaw foodways. Rooted in an Etuaptmumk-Two Eyed Seeing (E-TES) perspective, which acknowledges both Indigenous and Western ways of knowing, the project to date has featured seasonal food workshops, involvement in a children's summer math camp, a food safety training workshop for teens, and the development of an online toolkit. The project was guided by the Mi'kmaw principle of Netukulimk, which reinforces respect for Mother Earth and stewardship of the land, water, and air for subsequent generations. Involvement of community leaders has been key to successful planning and implementation. While technology plays an important role, lessons learned on the land are critical and will inform efforts to include language and ceremony in future programming. Dietitians are encouraged to support Indigenous-led land-based learning in support of the profession's commitment to reconciliation.


Assuntos
Inocuidade dos Alimentos , Humanos , Criança , Povos Indígenas/educação , Adolescente , Canadá , Nutricionistas/educação , Dietética/educação
20.
Can J Diet Pract Res ; : 1-10, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842094

RESUMO

Purpose: Patient dissatisfaction with hospital food is an important driver of poor food intake in hospitals. The objective of this study was to examine patient satisfaction with current menu offerings and explore patient preferences and values, in order to inform a patient-centred menu redesign.Methods: Between July and September 2021, a cross-sectional survey was distributed to inpatients receiving a lunch tray at Vancouver General Hospital, a large tertiary care centre in Vancouver, Canada. The survey was based on the Acute Care Hospital Foodservice Patient Satisfaction Questionnaire, with additional questions on food experience, factors impacting preferences for hospital meals, interest in plant-rich diets, and demographics.Results: The response rate was 5.5%, with 271 patients completing at least part of the survey. On a 5-point Likert scale, (5 - highest score; 1 - lowest score) satisfaction with food quality (mean = 3.09, p < 0.001) and the overall experience (mean = 3.54, p < 0.001) was lower than industry benchmark of 4, and qualitative feedback was generally negative. Open-ended responses indicated patients were interested in expanded cultural diversity in food provision, more fresh produce and better flavours, and were generally open to trying plant-rich foods.Conclusions: A number of opportunities for improvement were identified in this survey, which will inform an upcoming menu redesign in this institution.

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