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1.
Neurology ; 102(11): e209445, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38759137

RESUMO

BACKGROUND AND OBJECTIVES: Gene-gene interactions likely contribute to the etiology of multifactorial diseases such as cerebral venous thrombosis (CVT) and could be one of the main sources of known missing heritability. We explored Factor XI (F11) and ABO gene interactions among patients with CVT. METHODS: Patients with CVT of European ancestry from the large Bio-Repository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) international collaboration were recruited. Codominant modelling was used to determine interactions between genome-wide identified F11 and ABO genes with CVT status. RESULTS: We studied 882 patients with CVT and 1,205 ethnically matched control participants (age: 42 ± 15 vs 43 ± 12 years, p = 0.08: sex: 71% male vs 68% female, p = 0.09, respectively). Individuals heterozygous (AT) for the risk allele (T) at both loci (rs56810541/F11 and rs8176645/ABO) had a 3.9 (95% CI 2.74-5.71, p = 2.75e-13) increase in risk of CVT. Individuals homozygous (TT) for the risk allele at both loci had a 13.9 (95% CI 7.64-26.17, p = 2.0e-15) increase in risk of CVT. The presence of a non-O blood group (A, B, AB) combined with TT/rs56810541/F11 increased CVT risk by OR = 6.8 (95% CI 4.54-10.33, p = 2.00e15), compared with blood group-O combined with AA. DISCUSSION: Interactions between factor XI and ABO genes increase risk of CVT by 4- to 14-fold.


Assuntos
Sistema ABO de Grupos Sanguíneos , Fator XI , Humanos , Sistema ABO de Grupos Sanguíneos/genética , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Fator XI/genética , Trombose Venosa/genética , Trombose Intracraniana/genética , Epistasia Genética/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Galactosiltransferases
2.
Eur J Neurol ; : e16311, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38646961

RESUMO

BACKGROUND AND PURPOSE: Coma is an independent predictor of poor clinical outcomes in cerebral venous thrombosis (CVT). We aimed to describe the association of age, sex, and radiological characteristics of adult coma patients with CVT. METHODS: We used data from the international, multicentre prospective observational BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis) study. Only positively associated variables with coma with <10% missing data in univariate analysis were considered for the multivariate logistic regression model. RESULTS: Of the 596 adult patients with CVT (75.7% women), 53 (8.9%) patients suffered coma. Despite being a female-predominant disease, the prevalence of coma was higher among men than women (13.1% vs. 7.5%, p = 0.04). Transverse sinus thrombosis was least likely to be associated with coma (23.9% vs. 73.3%, p < 0.001). The prevalence of superior sagittal sinus thrombosis was higher among men than women in the coma sample (73.6% vs. 37.5%, p = 0.01). Men were significantly older than women, with a median (interquartile range) age of 51 (38.5-60) versus 40 (33-47) years in the coma (p = 0.04) and 44.5 (34-58) versus 37 (29-48) years in the non-coma sample (p < 0.001), respectively. Furthermore, an age- and superior sagittal sinus-adjusted multivariate logistic regression model found male sex (odds ratio = 1.8, 95% confidence interval [CI] = 1.0-3.4, p = 0.04) to be an independent predictor of coma in CVT, with an area under the receiver operating characteristic curve of 0.61 (95% CI = 0.52-0.68, p = 0.01). CONCLUSIONS: Although CVT is a female-predominant disease, men were older and nearly twice as likely to suffer from coma than women.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38264884

RESUMO

Data from literature show a cross-talk between the heart and liver during diseases which primarily involve one of the two organs, but data regarding this relationship are scant. Aim of this study was to investigate this relationship. In this narrative review we critically explored the most recent literature on this topic using PubMed and Medline and examining the most recent studies about liver involvement in heart failure and heart involvement in course of liver disease. Patients with acute and chronic heart failure and those who undergo heart transplatation (HT) manifest various signs of liver damage with a rate of incidence which is higher in candidates for left ventricular assist device. In presence of cardiogenic shock a very marked hepatocellular necrosis may occur while in the setting of chronic heart failure congestive hepatopathy and-or the so-called cardiac cirrhosis are observed. On the other side in presence of chronic liver disease and in case of liver transplantation (LT) heart functions may be altered and cirrhotic cardiomyopathy, which is a syndrome characterized by systolic, diastolic and electrophysiological abnormalities may occur. In this review we have analyzed the relationship between heart and liver disease, even in case of LT and HT. Furthermore we have underscored the effects of chronic alcoholism and of systemic disorders such as hemochromatosis and amyloidosis on both heart and liver.

4.
Eur J Heart Fail ; 26(1): 59-64, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38131253

RESUMO

AIMS: In the EXPLORER-HCM trial, mavacamten reduced left ventricular outflow tract obstruction (LVOTO) and improved functional capacity of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) patients. We sought to define the potential use of mavacamten by comparing real-world HOCM patients with those enrolled in EXPLORER-HCM and assessing their eligibility to treatment. METHODS AND RESULTS: We collected information on HOCM patients followed up at 25 Italian HCM outpatient clinics and with significant LVOTO (i.e. gradient ≥30 mmHg at rest or ≥50 mmHg after Valsalva manoeuvre or exercise) despite pharmacological or non-pharmacological therapy. Pharmacological or non-pharmacological therapy resolved LVOTO in 1044 (61.2%) of the 1706 HOCM patients under active follow-up, whereas 662 patients (38.8%) had persistent LVOTO. Compared to the EXPLORER-HCM trial population, these real-world HOCM patients were older (62.1 ± 14.3 vs. 58.5 ± 12.2 years, p = 0.02), had a lower body mass index (26.8 ± 5.3 vs. 29.7 ± 4.9 kg/m2 , p < 0.0001) and a more frequent history of atrial fibrillation (21.5% vs. 9.8%, p = 0.027). At echocardiography, they had lower left ventricular ejection fraction (LVEF, 66 ± 7% vs. 74 ± 6%, p < 0.0001), higher left ventricular outflow tract gradients at rest (60 ± 27 vs. 52 ± 29 mmHg, p = 0.003), and larger left atrial volume index (49 ± 16 vs. 40 ± 12 ml/m2 , p < 0.0001). Overall, 324 (48.9%) would have been eligible for enrolment in the EXPLORER-HCM trial and 339 (51.2%) for treatment with mavacamten according to European guidelines. CONCLUSIONS: Real-world HOCM patients differ from the EXPLORER-HCM population for their older age, lower LVEF and larger atrial volume, potentially reflecting a more advanced stage of the disease. About half of real-world HOCM patients were found eligible to mavacamten.


Assuntos
Benzilaminas , Cardiomiopatia Hipertrófica , Insuficiência Cardíaca , Uracila , Humanos , Cardiomiopatia Hipertrófica/tratamento farmacológico , Volume Sistólico , Uracila/análogos & derivados , Função Ventricular Esquerda
5.
Bioresour Technol ; 390: 129880, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37852509

RESUMO

The environmental concerns regarding fossil plastics call for alternative biopolymers such as polyhydroxyalkanoates (PHAs) whose manufacturing costs are however still too elevated. Autotrophic microbes like Cupriavidus necator, able to convert CO2 and H2 into PHAs, offer an additional strategy. Typically, the preferred source for CO2 and H2 are expensive pure gases or syngas, which has toxic compounds for most PHAs-accumulating strains. In this work, for the first time, H2 and CO2 originating from an acidogenic reactor were converted autotrophically into poly(3-hydroxybutyrate) P(3HB). During the first stage, a mixed microbial community continuously catabolized melon waste into H2 (26.7 %) and CO2 (49.2 %) that were then used in a second bioreactor by C. necator DSM 545 to accumulate 1.7 g/L P(3HB). Additionally, the VFAs (13 gCOD/L) produced during acidogenesis were processed into 2.7 g/L of P(3HB-co-3HV). This is the first proof-of-concept of using acidogenic-derived H2 and CO2 from fruit waste to produce PHAs.


Assuntos
Cupriavidus necator , Poli-Hidroxialcanoatos , Poli-Hidroxialcanoatos/metabolismo , Dióxido de Carbono , Fermentação , Frutas/metabolismo , Reatores Biológicos , Cupriavidus necator/metabolismo
6.
Angew Chem Int Ed Engl ; 62(31): e202303585, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37260054

RESUMO

Here, we report a general approach to the synthesis of the difluoroalkyl bicycloalkanes (CF2 -BCAs), as structural surrogates of aryl ketones and ethers. The chemistry is driven by a dihydrobenzoacridine photocatalyst, that engages in a catalytic electron-donor acceptor (EDA) complex, or directly reduces the fluorinated substrate. These two convergent manifolds lead to the generation of the R-CF2 radical, that reacts with the [1.1.1]- or [3.1.1.]-propellane. The method is extremely general, and extendable to complex bioactive molecules (30 examples, up to 87 % yield). The structural features of the CF2 -BCP hybrid bioisostere were investigated by single crystal X-ray. Finally, we synthesised a CF2 -BCP analogue of a Leukotriene A4 hydrolase inhibitor, replacing the original aryl ether motif. In silico docking studies indicated that this new analogue maintains the same arrangement within the enzyme pocket, profiling the use of the CF2 -BCA hybrid bioisostere in medicinal chemistry settings.

7.
Eur Spine J ; 32(10): 3360-3369, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37336795

RESUMO

PURPOSE: Intraoperative muscle motor evoked potentials (m-MEPs) are widely used in spinal surgery with the aim of identifying a damage to spinal cord at a reversible stage. Generally, lower limb m-MEPs are recorded from abductor hallucis [AH] and the tibialis anterior [TA]. The purpose of this work is to study an unselected population by recording the m-MEPs from TA, AH and extensor digitorum brevis (EDB), with the aim of identifying the most adjustable and stable muscles responses intraoperatively. METHODS: Transcranially electrically induced m-MEPs were intraoperative recorded in a total of 107 surgical procedures. m-MEPs were recorded by a needle electrode placed in the muscle from TA, AH and EDB muscles in the lower extremities. RESULTS: Overall monitorability (i.e., at least 1 Lower Limb m-MEP recordable) was 100/107 (93.5%). In the remaining 100 surgeries in 3 cases, the only muscle that could be recorded at baseline was one AH, and in other 2 the EDB. Persistence (i.e., the recordability of m-MEP from baseline to the end of surgery) was 88.7% for TA, 89.8% for AH and 93.8% for EDB. CONCLUSION: In our series, EDB m-MEPs have demonstrated a recordability superior to TA and a stability similar to AH. The explanations may be different and range from changes in the excitability of the cortical motor neuron to the different sensitivity to ischemia of the spinal motor neuron. EDB can be used alternatively or can be added to TA and AH as a target muscle of the lower limb in spinal surgery.


Assuntos
Monitorização Intraoperatória , Medula Espinal , Humanos , Monitorização Intraoperatória/métodos , Medula Espinal/cirurgia , Coluna Vertebral/cirurgia , Músculo Esquelético/fisiologia , Procedimentos Neurocirúrgicos , Potencial Evocado Motor/fisiologia
8.
Nat Synth ; 9622023 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-37325160

RESUMO

Information gained from in-depth mechanistic investigations can be used to control the selectivity of reactions, leading to the expansion of the generality of synthetic processes and the discovery of new reactivity. Here, we investigate the mechanism of light-driven [2+2] heterocycloadditions (Paternò-Büchi reactions) between indoles and ketones to develop insight into these processes. Using ground-state UV-Vis absorption and transient absorption spectroscopy (TAS), together with DFT calculations, we found that the reactions can proceed via an exciplex or electron-donor-acceptor (EDA) complex, which are key intermediates in determining the stereoselectivity of the reactions. We used this discovery to control the diastereoselectivity of the reactions, gaining access to previously inaccessible diastereoisomeric variants. When moving from 370 to 456 nm irradiation, the EDA complex is increasingly favoured, and the diastereomeric ratio (d.r.) of the product moves from >99:<1 to 47:53. In contrast, switching from methyl to ipropyl substitution favours the exciplex intermediate, reversing the d.r. from 89:11 to 16:84. Our study shows how light and steric parameters can be rationally used to control the diastereoselectivity of photoreactions, creating mechanistic pathways to previously inaccessible stereochemical variants.

9.
Eur Stroke J ; 8(1): 344-350, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-37021156

RESUMO

Background: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke in young adults. We aimed to determine the impact of age, gender and risk factors (including sex-specific) on CVT onset. Methods: We used data from the BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis), a multicentre multinational prospective observational study on CVT. Composite factors analysis (CFA) was performed to determine the impact on the age of CVT onset in males and females. Results: A total of 1309 CVT patients (75.3% females) aged ⩾18 years were recruited. The overall median (IQR-interquartile range) age for males and females was 46 (35-58) years and 37 (28-47) years (p < 0.001), respectively. However, the presence of antibiotic-requiring sepsis (p = 0.03, 95% CI 27-47 years) among males and gender-specific risk factors like pregnancy (p < 0.001, 95% CI 29-34 years), puerperium (p < 0.001, 95% CI 26-34 years) and oral contraceptive use (p < 0.001, 95% CI 33-36 years) were significantly associated with earlier onset of CVT among females. CFA demonstrated a significantly earlier onset of CVT in females, ~12 years younger, in those with multiple (⩾1) compared to '0' risk factors (p < 0.001, 95% CI 32-35 years). Conclusions: Women suffer CVT 9 years earlier in comparison to men. Female patients with multiple (⩾1) risk factors suffer CVT ~12 years earlier compared to those with no identifiable risk factors.


Assuntos
Trombose Intracraniana , Trombose Venosa , Masculino , Gravidez , Adulto Jovem , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Trombose Venosa/epidemiologia , Idade de Início , Trombose Intracraniana/epidemiologia , Fatores de Risco
10.
Polymers (Basel) ; 14(24)2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36559896

RESUMO

Traditional plastics represent a tremendous threat to the environment because of increases in polluting manufacturing as well as their very extended degradation time. Polyhydroxyalkanoates (PHAs) are polymers with similar performance to plastic but are compostable and synthesizable from renewable sources and therefore could be a replacement for fossil-based plastics. However, their production costs are still too high, thus demanding the investigation of new and cheap substrates. In this sense, agricultural wastes are attractive because they are inexpensive and largely available. Specifically, fruit and vegetables are rich in sugars that could be fermented into PHAs. In this work two strains, Cupriavidus necator DSM 545 and Hydrogenophaga pseudoflava DSM 1034, well-known PHA-producing microbes, were screened for their ability to grow and accumulate PHAs. Ten different fruit and vegetable processing waste streams, never before reported in combination with these strains, were tested. Residues from red apple and melon were found to be the most suitable feedstocks for PHA production. Under specific selected conditions, C. necator DSM 545 accumulated up to 7.4 and 4.3 g/L of 3-hydroxybutyrate (3HB) from red apple and melon, respectively. Copolymer production was also obtained from melon. These results confirm the attractiveness of food processing waste as a promising candidate for PHA production. Ultimately, these novel substrates draw attention for future studies on process optimization and upscaling with C. necator.

12.
Stud Health Technol Inform ; 297: 143-150, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36073389

RESUMO

Home adaptation is a practice that addresses accessibility issues in the domestic environment of disabled people, introducing modifications to the spatial environment or devices which improve their autonomy and wellbeing, and that of their caregivers. Protocols developed to define the right adaptations for each home mainly rely on checklists to verify the normative compliance of the physical environment to predefined accessibility standards. However, these protocols fail to address the complexity of the social, cultural, and economic dimensions that structure the person-environment relationship, thus compromising the efficacy of the adaptations. The excessive rigidity of such approach relates to the current debate on the limits of Universal Design when applied to the domestic environment, and especially when directed to people with specific needs. As an example of a more productive approach, this essay illustrates ADA, a public funded action-research project that proposes home adaptations for severely disabled people. The paper discusses the innovative strategy of ADA, based on a high level of personalization, and its main tactics: interdisciplinarity, relational setting, and centrality of activities, both in the assessment of the users' profiles and spaces, and in the design of the adaptations. This essay also evaluates the impact of the project, showing how in specific domains, such as those of ADA, personalization is the key to achieve the inclusive and sustainable goals of Universal Design.


Assuntos
Pessoas com Deficiência , Objetivos , Humanos , Itália
13.
J Am Chem Soc ; 144(31): 14021-14025, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35881505

RESUMO

As the natural-born photoelectrolyzer for oxygen delivery, photosystem II (PSII) is hardly replicated with man-made constructs. However, building on the "quantasome" hypothesis ( Science 1964, 144, 1009-1011), PSII mimicry can be pared down to essentials by shaping a photocatalytic ensemble (from the Greek term "soma" = body) where visible-light quanta trigger water oxidation. PSII-inspired quantasomes (QS) readily self-assemble into hierarchical photosynthetic nanostacks, made of bis-cationic perylenebisimides (PBI2+) as chromophores and deca-anionic tetraruthenate polyoxometalates (Ru4POM) as water oxidation catalysts ( Nat. Chem. 2019, 11, 146-153). A combined supramolecular and click-chemistry strategy is used herein to interlock the PBI-QS with tetraethylene glycol (TEG) cross-linkers, yielding QS-TEGlock with increased water solvation, controlled growth, and up to a 340% enhancement of the oxygenic photocurrent compared to the first generation QS, as probed on 3D-inverse opal indium tin oxide electrodes at 8.5 sun irradiance (λ > 450 nm, 1.28 V vs RHE applied bias, TOFmax = 0.096 ± 0.005 s-1, FEO2 > 95%). Action spectra, catalyst mass-activity, light-management, photoelectrochemical impedance spectroscopy (PEIS) together with Raman mapping of TEG-templated hydration shells point to a key role of the cross-linked PBI/Ru4POM nanoarrays, where the interplay of hydrophilic/hydrophobic domains is reminiscent of PSII-rich natural thylakoids.


Assuntos
Oxigênio , Fotossíntese , Humanos , Imidas , Luz , Oxirredução , Oxigênio/química , Perileno/análogos & derivados , Complexo de Proteína do Fotossistema II/química , Água/química
14.
J Neurol Neurosurg Psychiatry ; 93(7): 686-692, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35508372

RESUMO

OBJECTIVE: To explore the impact of antithrombotic therapy discontinuation in the postacute phase of cervical artery dissection (CeAD) on the mid-term outcome of these patients. METHODS: In a cohort of consecutive patients with first-ever CeAD, enrolled in the setting of the multicentre Italian Project on Stroke in Young Adults Cervical Artery Dissection, we compared postacute (beyond 6 months since the index CeAD) outcomes between patients who discontinued antithrombotic therapy and patients who continued taking antithrombotic agents during follow-up. Primary outcome was a composite of ischaemic stroke and transient ischaemic attack. Secondary outcomes were (1) Brain ischaemia ipsilateral to the dissected vessel and (2) Recurrent CeAD. Associations with the outcome of interest were assessed by the propensity score (PS) method. RESULTS: Of the 1390 patients whose data were available for the outcome analysis (median follow-up time in patients who did not experience outcome events, 36.0 months (25th-75th percentile, 62.0)), 201 (14.4%) discontinued antithrombotic treatment. Primary outcome occurred in 48 patients in the postacute phase of CeAD. In PS-matched samples (201 vs 201), the incidence of primary outcomes among patients taking antithrombotics was comparable with that among patients who discontinued antithrombotics during follow-up (5.0% vs 4.5%; p(log rank test)=0.526), and so was the incidence of the secondary outcomes ipsilateral brain ischaemia (4.5% vs 2.5%; p(log rank test)=0.132) and recurrent CeAD (1.0% vs 1.5%; p(log rank test)=0.798). CONCLUSIONS: Discontinuation of antithrombotic therapy in the postacute phase of CeAD does not appear to increase the risk of brain ischaemia during follow-up.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Dissecação da Artéria Vertebral , Artérias , Isquemia Encefálica/complicações , Fibrinolíticos/uso terapêutico , Humanos , Acidente Vascular Cerebral/complicações , Dissecação da Artéria Vertebral/complicações , Dissecação da Artéria Vertebral/tratamento farmacológico , Dissecação da Artéria Vertebral/epidemiologia , Adulto Jovem
15.
Org Lett ; 24(16): 2961-2966, 2022 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-35437017

RESUMO

A mild light-driven protocol for the direct alkylation of phenols is reported. The process is driven by the photochemical activity of a halogen-bonded complex formed upon complexation of the in situ generated electron-rich phenolate anion with the α-iodosulfone. The reaction proceeds rapidly (10 min) under microfluidic conditions, delivering a wide variety of ortho-alkylated products (27 examples, up to 97% yield, >20:1 regioselectivity, on a gram scale), including densely functionalized bioactive phenol derivatives.


Assuntos
Halogênios , Fenóis , Alquilação , Microfluídica , Fenol
16.
Front Neurol ; 13: 834469, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35309582

RESUMO

Background: Acute ischemic stroke (AIS) is a possible complication of coronavirus disease 2019 (COVID-19) infection. Although peculiar clinical features and underlying specific mechanisms of thrombogenesis have been suggested so far, there is no consensus on the appropriate vascular preventive drug regimen in patients with COVID-19. Aim and Methods: From a larger clinical series of consecutive acute ischemic strokes related to COVID-19 admitted to three cerebrovascular units in Northern Italy, herein, we describe the clinical features of a subgroup of patients in whom stroke occurred despite therapeutic anticoagulation. Results: A total of seventeen/80 AIS related to COVID-19 (21.2%) occurred in anticoagulated patients. Although no blood level was available for Direct Oral AntiCoagulant, the drug dosage was appropriate according to guidelines. Their National Institute of Health Stroke Scale (NIHSS) at admission was 12.0 (SD = 7.4) and 58.8% of them had evidence of large vessel occlusion. The case fatality rate was as high as 64.7%. Discussion and Conclusions: The occurrence of an anticoagulation failure seems to be increased in the setting of COVID-19 infection, with worse clinical outcomes if compared to non-COVID-19 related ischemic strokes. We discuss the diagnostic and therapeutic implications of such evidence, suggesting that some arterial thrombotic complications might be either resistant to or independent of the anticoagulation effect.

17.
Int J Stroke ; 17(9): 1013-1020, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35318878

RESUMO

BACKGROUND: Hematoma expansion (HE) is common and associated with poor outcome in intracerebral hemorrhage (ICH) with unclear symptom onset (USO). AIMS: We tested the association between non-contrast computed tomography (NCCT) markers and HE in this population. METHODS: Retrospective analysis of patients with primary spontaneous ICH admitted at five centers in the United States and Italy. Baseline NCCT was analyzed for presence of the following markers: intrahematoma hypodensities, heterogeneous density, blend sign, and irregular shape. Variables associated with HE (hematoma growth > 6 mL and/or > 33% from baseline to follow-up imaging) were explored with multivariable logistic regression. RESULTS: Of 2074 patients screened, we included 646 subjects (median age = 75, 53.9% males), of whom 178 (27.6%) had HE. Hypodensities (odds ratio (OR) = 2.67, 95% confidence interval (CI) = 1.79-3.98), heterogeneous density (OR = 2.16, 95% CI = 1.46-3.21), blend sign (OR = 2.28, 95% CI = 1.38-3.75) and irregular shape (OR = 1.82, 95% CI = 1.21-2.75) were independently associated with a higher risk of HE, after adjustment for confounders (ICH volume, anticoagulation, and time from last seen well (LSW) to NCCT). Hypodensities had the highest sensitivity for HE (0.69), whereas blend sign was the most specific marker (0.90). All NCCT markers were more frequent in early presenters (time from LSW to NCCT ⩽ 6 h, n = 189, 29.3%), and more sensitive in this population as well (hypodensities had 0.77 sensitivity). CONCLUSION: NCCT markers are associated with HE in ICH with USO. These findings require prospective replication and suggest that NCCT features may help the stratification of HE in future studies on USO patients.


Assuntos
Acidente Vascular Cerebral , Masculino , Humanos , Feminino , Estudos Retrospectivos , Estudos Prospectivos , Acidente Vascular Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/complicações , Hematoma/diagnóstico por imagem , Hematoma/complicações , Biomarcadores , Anticoagulantes
18.
Oncogene ; 41(11): 1563-1575, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35091681

RESUMO

We investigated the role of the NFE2L3 transcription factor in inflammation-induced colorectal cancer. Our studies revealed that Nfe2l3-/- mice exhibit significantly less inflammation in the colon, reduced tumor size and numbers, and skewed localization of tumors with a more pronounced decrease of tumors in the distal colon. CIBERSORT analysis of RNA-seq data from normal and tumor tissue predicted a reduction in mast cells in Nfe2l3-/- animals, which was confirmed by toluidine blue staining. Concomitantly, the transcript levels of Il33 and Rab27a, both important regulators of mast cells, were reduced and increased, respectively, in the colorectal tumors of Nfe2l3-/- mice. Furthermore, we validated NFE2L3 binding to the regulatory sequences of the IL33 and RAB27A loci in human colorectal carcinoma cells. Using digital spatial profiling, we found that Nfe2l3-/- mice presented elevated FOXP3 and immune checkpoint markers CTLA4, TIM3, and LAG3, suggesting an increase in Treg counts. Staining for CD3 and FOXP3 confirmed a significant increase in immunosuppressive Tregs in the colon of Nfe2l3-/- animals. Also, Human Microbiome Project (HMP2) data showed that NFE2L3 transcript levels are higher in the rectum of ulcerative colitis patients. The observed changes in the tumor microenvironment provide new insights into the molecular differences regarding colon cancer sidedness. This may be exploited for the treatment of early-onset colorectal cancer as this emerging subtype primarily displays distal/left-sided tumors.


Assuntos
Neoplasias Colorretais , Microambiente Tumoral , Animais , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Neoplasias Colorretais/genética , Fatores de Transcrição Forkhead , Humanos , Inflamação/genética , Interleucina-33 , Camundongos , Linfócitos T Reguladores , Microambiente Tumoral/genética
19.
Neuroradiology ; 64(7): 1367-1372, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35034151

RESUMO

PURPOSE: Intracerebral hemorrhage (ICH) is an uncommon but deadly event in patients with COVID-19 and its imaging features remain poorly characterized. We aimed to describe the clinical and imaging features of COVID-19-associated ICH. METHODS: Multicenter, retrospective, case-control analysis comparing ICH in COVID-19 patients (COV19 +) versus controls without COVID-19 (COV19 -). Clinical presentation, laboratory markers, and severity of COVID-19 disease were recorded. Non-contrast computed tomography (NCCT) markers (intrahematoma hypodensity, heterogeneous density, blend sign, irregular shape fluid level), ICH location, and hematoma volume (ABC/2 method) were analyzed. The outcome of interest was ultraearly hematoma growth (uHG) (defined as NCCT baseline ICH volume/onset-to-imaging time), whose predictors were explored with multivariable linear regression. RESULTS: A total of 33 COV19 + patients and 321 COV19 - controls with ICH were included. Demographic characteristics and vascular risk factors were similar in the two groups. Multifocal ICH and NCCT markers were significantly more common in the COV19 + population. uHG was significantly higher among COV19 + patients (median 6.2 mL/h vs 3.1 mL/h, p = 0.027), and this finding remained significant after adjustment for confounding factors (systolic blood pressure, antiplatelet and anticoagulant therapy), in linear regression (B(SE) = 0.31 (0.11), p = 0.005). This association remained consistent also after the exclusion of patients under anticoagulant treatment (B(SE) = 0.29 (0.13), p = 0.026). CONCLUSIONS: ICH in COV19 + patients has distinct NCCT imaging features and a higher speed of bleeding. This association is not mediated by antithrombotic therapy and deserves further research to characterize the underlying biological mechanisms.


Assuntos
COVID-19 , Anticoagulantes , Biomarcadores , COVID-19/complicações , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Hematoma/diagnóstico por imagem , Humanos , Estudos Retrospectivos
20.
J Sci Food Agric ; 102(2): 844-850, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34231921

RESUMO

BACKGROUND: Beyond nutrition, fruits and vegetables can be considered as natural sources of bioactive molecules, for which beneficial effects on human health are widely recognised. To improve food quality, soilless growing systems could represent a good strategy for promoting a sustainable food production chain, although the nutritional and nutraceutical properties of their products should be investigated in depth. The main quality traits and the volatile and non-volatile secondary metabolites of Solanum lycopersicum L., Petroselinum crispum (Mill.) Fuss and Ocimun basilicum L. grown in an aquaponics system and in organic farming were quantified and compared. RESULTS: On a fresh basis, soil-grown P. crispum and O. basilicum showed significantly higher total phenolics and antioxidant activity compared to aquaponic crops, whereas, on a dry basis, both plants showed opposite results. Soil-grown S. lycopersicum was significantly richer in total phenolics, whereas the aquaponic type showed a higher antioxidant activity. Aquaponics induced the accumulation of resveratrol in P. crispum, rosmarinic acid and myricetin in O. basilicum, and lycopene in S. lycopersicum. Among the volatile compounds, in O. basilicum, linalool was the main constituent in both treatments, whereas τ-cadinol represented the second constituent in aquaponic crops. The volatile profiles of P. crispum did not differ significantly between the two cultivation methods. CONCLUSION: The overall quality of organic and aquaponics cultures appeared to be comparable. The results showed that aquaponic farming method can be an innovative, rapid and sustainable way of producing quality food. © 2021 Society of Chemical Industry.


Assuntos
Frutas/química , Frutas/crescimento & desenvolvimento , Hidroponia/métodos , Compostos Fitoquímicos/química , Verduras/química , Verduras/crescimento & desenvolvimento , Antioxidantes/química , Produtos Agrícolas/química , Produtos Agrícolas/crescimento & desenvolvimento , Qualidade dos Alimentos , Hidroponia/instrumentação , Agricultura Orgânica , Fenóis/química
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