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1.
Cureus ; 16(5): e59452, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38826987

RESUMO

Patients with Marfan syndrome have a constellation of clinical features and a heterogeneous phenotype. The purpose of this study is to report a 47-year-old male patient with an unusual variant in the FBN1 gene causing Marfan syndrome. The patient with musculoskeletal, cardiovascular, and ocular findings compatible with Marfan syndrome had an unusual pathogenic mutation on the FBN1 gene. The patient was examined by at least one of the authors (NJI). The patient's clinical findings were compatible with Marfan syndrome. Our patient had a unique mutation in the FBN1 gene (c.8054A>G p.His2685Arg) located on exon 65. Next-generation sequencing was done using the Invitae panel. This variant was categorized as one of uncertain significance. This patient's variant on the FBN1 gene leading to the syndrome has scant data associated with it and this is the first time it is reported from Puerto Rico.

3.
Chemistry ; : e202401428, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717583

RESUMO

Sn3P8N16 combines the structural versatility of nitridophosphates and Sn within one compound. It was synthesized as dark gray powder in a high-pressure high-temperature reaction at 800 °C and 6 GPa from Sn3N4 and P3N5. The crystal structure was elucidated from single-crystal diffraction data (space group C2/m (no. 12), a = 12.9664(4), b = 10.7886(4), c = 4.8238(2) Å, ß = 109.624(1)°) and shows a 3D-network of PN4 tetrahedra, incorporating Sn in oxidation states +II and +IV. The Sn cations are located within eight-membered rings of vertex-sharing PN4 tetrahedra, stacked along the [001] direction. A combination of solid-state nuclear magnetic resonance spectroscopy, 119Sn Mössbauer spectroscopy and density functional theory calculations was used to confirm the mixed oxidation of Sn. Temperature-dependent powder X-ray diffraction measurements reveal a low thermal expansion of 3.6 ppm/K up to 750 °C, beyond which Sn3P8N16 starts to decompose.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38747693

RESUMO

The use of algae as feedstock for industrial purposes, such as in bioethanol production, is desirable. During a search for new agarolytic marine bacteria, a novel Gram-stain-negative, strictly aerobic, and agarolytic bacterium, designated as TS8T, was isolated from algae in the harbour of the island of Susak, Croatia. The cells were rod-shaped and motile. The G+C content of the sequenced genome was 38.6 mol%. Growth was observed at 11-37 °C, with 0.5-13 % (w/v) NaCl, and at pH 6.0-9.0. The main fatty acids were summed feature 3 (C16 : 1 ω6c and/or C16 : 1 ω7c), summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), and C16 : 0. The main respiratory quinone was ubiquinone-8. The major polar lipids were phosphatidylethanolamine and phosphatidylglycerol. Analysis of 16S rRNA gene sequences indicated that the newly isolated strain belongs to the genus Catenovulum. Based on 16S rRNA gene sequence data, strain TS8T is closely related to Catenovulum sediminis D2T (95.7 %), Catenovulum agarivorans YM01T (95.0 %), and Catenovulum maritimum Q1T (93.2 %). Digital DNA-DNA hybridization values between TS8T and the other Catenovulum strains were below 25 %. Based on genotypic, phenotypic, and phylogenetic data, strain TS8T represents a new species of the genus Catenovulum, for which the name Catenovulum adriaticum sp. nov. is proposed. The type strain is TS8T (=DSM 114830T=NCIMB 15451T).


Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Ubiquinona , RNA Ribossômico 16S/genética , Ácidos Graxos/análise , Ácidos Graxos/química , Croácia , DNA Bacteriano/genética , Fosfolipídeos/química , Fosfolipídeos/análise , Hibridização de Ácido Nucleico , Fosfatidiletanolaminas
5.
J Am Coll Cardiol ; 83(21): 2052-2062, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38777509

RESUMO

BACKGROUND: The prognostic significance of various microvascular injury (MVI) patterns after ST-segment elevation myocardial infarction (STEMI) is not well known. OBJECTIVES: This study sought to investigate the prognostic implications of different MVI patterns in STEMI patients. METHODS: The authors analyzed 1,109 STEMI patients included in 3 prospective studies. Cardiac magnetic resonance (CMR) was performed 3 days (Q1-Q3: 2-5 days) after percutaneous coronary intervention (PCI) and included late gadolinium enhancement imaging for microvascular obstruction (MVO) and T2∗ mapping for intramyocardial hemorrhage (IMH). Patients were categorized into those without MVI (MVO-/IMH-), those with MVO but no IMH (MVO+/IMH-), and those with IMH (IMH+). RESULTS: MVI occurred in 633 (57%) patients, of whom 274 (25%) had an MVO+/IMH- pattern and 359 (32%) had an IMH+ pattern. Infarct size was larger and ejection fraction lower in IMH+ than in MVO+/IMH- and MVO-/IMH- (infarct size: 27% vs 19% vs 18% [P < 0.001]; ejection fraction: 45% vs 50% vs 54% [P < 0.001]). During a median follow-up of 12 months (Q1-Q3: 12-35 months), a clinical outcome event occurred more frequently in IMH+ than in MVO+/IMH- and MVO-/IMH- subgroups (19.5% vs 3.6% vs 4.4%; P < 0.001). IMH+ was the sole independent MVI parameter predicting major adverse cardiovascular events (HR: 3.88; 95% CI: 1.93-7.80; P < 0.001). CONCLUSIONS: MVI is associated with future adverse outcomes only in patients with a hemorrhagic phenotype (IMH+). Patients with only MVO (MVO+/IMH-) had a prognosis similar to patients without MVI (MVO-/IMH-). This highlights the independent prognostic importance of IMH in assessing and managing risk after STEMI.


Assuntos
Imagem Cinética por Ressonância Magnética , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Imagem Cinética por Ressonância Magnética/métodos , Estudos Prospectivos , Idoso , Prognóstico , Microcirculação , Microvasos/diagnóstico por imagem , Microvasos/lesões , Microvasos/patologia
6.
Anesthesiology ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775960

RESUMO

While effects of general anesthesia on neuronal activity in the human neonatal brain are incompletely understood, electroencephalography (EEG) provides some insight and may identify age-dependent differences. A systematic search (MEDLINE, Embase, PUBMED, Cochrane Library to November 2023) retrieved English language publications reporting EEG during general anesthesia for cardiac or non-cardiac surgery in term neonates (37 to 44 weeks post-menstrual age). Data were extracted and risk of bias (ROBINS-I Cochrane tool) and quality of evidence (GRADE checklist) assessed. From 1155 abstracts, nine publications (157 neonates; 55.7% male) fulfilled eligibility criteria. Data were limited and study quality was very low. The occurrence of discontinuity, a characteristic pattern of alternating higher and lower amplitude EEG segments, was reported with general anesthesia (94 of 119 neonates, six publications) and with hypothermia (23 of 23 neonates, two publications). Decreased power in the delta (0.5-4Hz) frequency range was also reported with increasing anesthetic dose (39 neonates; three publications). While evidence gaps were identified, both increasing sevoflurane concentration and decreasing temperature are associated with increasing discontinuity.

7.
bioRxiv ; 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38712292

RESUMO

Tumor-associated neutrophils (TANs) have been shown to promote immunosuppression and tumor progression, and a high TAN frequency predicts poor prognosis in triple-negative breast cancer (TNBC). Dysregulation of CREB binding protein (CBP)/P300 function has been observed with multiple cancer types. The bromodomain (BRD) of CBP/P300 has been shown to regulate its activity. In this study, we found that IACS-70654, a novel and selective CBP/P300 BRD inhibitor, reduced TANs and inhibited the growth of neutrophil-enriched TNBC models. In the bone marrow, CBP/P300 BRD inhibition reduced the tumor-driven abnormal differentiation and proliferation of neutrophil progenitors. Inhibition of CBP/P300 BRD also stimulated the immune response by inducing an IFN response and MHCI expression in tumor cells and increasing tumor-infiltrated CTLs. Moreover, IACS-70654 improved the response of a neutrophil-enriched TNBC model to docetaxel and immune checkpoint blockade. This provides a rationale for combining a CBP/P300 BRD inhibitor with standard-of-care therapies in future clinical trials for neutrophil-enriched TNBC.

8.
Environ Microbiome ; 19(1): 35, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38812054

RESUMO

BACKGROUND: Extreme weather events induced by climate change, particularly droughts, have detrimental consequences for crop yields and food security. Concurrently, these conditions provoke substantial changes in the soil bacterial microbiota and affect plant health. Early recognition of soil affected by drought enables farmers to implement appropriate agricultural management practices. In this context, interpretable machine learning holds immense potential for drought stress classification of soil based on marker taxa. RESULTS: This study demonstrates that the 16S rRNA-based metagenomic approach of Differential Abundance Analysis methods and machine learning-based Shapley Additive Explanation values provide similar information. They exhibit their potential as complementary approaches for identifying marker taxa and investigating their enrichment or depletion under drought stress in grass lineages. Additionally, the Random Forest Classifier trained on a diverse range of relative abundance data from the soil bacterial micobiome of various plant species achieves a high accuracy of 92.3 % at the genus rank for drought stress prediction. It demonstrates its generalization capacity for the lineages tested. CONCLUSIONS: In the detection of drought stress in soil bacterial microbiota, this study emphasizes the potential of an optimized and generalized location-based ML classifier. By identifying marker taxa, this approach holds promising implications for microbe-assisted plant breeding programs and contributes to the development of sustainable agriculture practices. These findings are crucial for preserving global food security in the face of climate change.

9.
Anal Chim Acta ; 1311: 342657, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38816150

RESUMO

BACKGROUND: The latest chromatographic retention models are capable of accurately describe the dependencies of retention over a wide range of experimental conditions. By using a suitable conversion, these models can be transformed into equations expressing the optimization criteria as function of multiples variables. Even though that theoretical models significantly reduce the experimental requirements for optimizations, these models have been barely used. Instead, most optimizations rely on empirical exploration of the relationships between criterions and variables. There is a need for a strategy to reduce the required number of experiments in multivariated optimization of separations, and Fundamental Models offer a clear opportunity for addressing it. RESULTS: A Fundamental Model is used to give the simultaneous dependence of chromatographic retention of seven ionizable pesticides on the three variables: solvent composition, temperature and pH (w, T, pH). Based on few experiments, the 10 parameters required to predict the chromatographic retention of those compounds, taken as model analytes, can be obtained. Two mathematical treatments to convert retentions into resolutions between pairs are used: one considering extracolumn dispersions and other neglecting these contributions. Using the Overlapped Resolutions Maps, extended to four dimensions, two optimal conditions can be found for the two different mathematical conversions. Chromatographic conditions were empirically evaluated obtaining the best results for the optimization considering extracolumn dispersions, proving that this condition is a true optimal. It was demonstrated that any small shift in any of the variables from this true optimal leads to a loss in resolution. SIGNIFICANCE: Fundamental Models describing chromatographic retention as a simultaneous function of multiple variables are nowadays very accurate. In this work is demonstrated that these models are useful not only to predict retentions, but also to optimize separations, even in the more challenging mode: isocratic, isothermal and iso-pH. However, the success in the optimization procedure depends also on the proper definition of the mathematical conversion of the Fundamental Models into optimization criteria.

10.
Qual Health Res ; : 10497323241239487, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38648467

RESUMO

Supporting ageing in place, quality of life, and activity engagement are public health priorities for people with dementia. The importance of maintaining opportunities for meaningful activities has been widely acknowledged for those with dementia in long-term care, but little is known about what makes activities meaningful for, and how they are experienced by, people with different types of dementia in their own homes. This study used focussed ethnographic methods to explore the motivations and meanings of everyday activity engagement within the homes of 10 people with memory-led Alzheimer's disease and 10 people with posterior cortical atrophy. While participants' interactions with their everyday environments were challenged by their diagnoses, they were all finding ways to continue meaning-making via various activities. The main findings are encapsulated in three themes: (1) The fun and the function of activities; (2) Reciprocities of care, and (3) The constitution and continuity of (a changing) self. Ongoing engagement with both fun and functional activities offered participants living with different dementias opportunities to connect with others, to offer care and support (as well as receive it), and to maintain a sense of self and identity. Implications are discussed regarding the development and delivery of tailored interventions and support to enable continued engagement in meaningful activities for people with different types of dementia living in the community.

11.
Cureus ; 16(3): e55632, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38586746

RESUMO

Previous studies have reported that patients with retinitis pigmentosa (RP) may develop open-angle and angle-closure glaucoma. We conducted a chart review of patients with RP. Two siblings with RP associated with a mutation in the PDE6B gene (c. 1540del, p.Leu514Trpfs*61) developed cystoid macular edema (CME) as part of the disease. For this reason, they both underwent intravitreal steroid injections. Both brothers developed steroid-induced glaucoma (SIG). Despite undergoing maximal medical therapy, they underwent seton implants to control their intraocular pressure. A third female patient with RP due to a mutation in the RPGR gene underwent cataract surgery. Topical steroids were prescribed and developed SIG. Increased intraocular pressure remains a complication of topical, injected, and systemic steroids. However, steroids may be needed to treat post-operatively and patients with CME. This case series unveils a complex association between RP and key comorbidities in these patients, with a focus on cataracts, glaucoma, and macular edema. Cataract surgery in patients with RP shows a link to the emergence of glaucoma, particularly in those with RPGR and PDE6B gene mutations, revealing a novel association with PDE6B mutations not previously documented. Furthermore, the paper explores a unique parallel with Schwartz-Matsuo syndrome, suggesting that patients with RP undergoing cataract surgery may develop increased intraocular pressure due to an outflow disturbance akin to Schwartz syndrome. This novel perspective deepens our understanding of the pathophysiological mechanisms governing intraocular pressure dynamics in patients with RP. To our knowledge, this is the first report of steroid-induced glaucoma in patients with RP due to mutations in the PDE6B gene. Intraocular pressure evaluation remains of utmost importance in the follow-up of patients with the disease.

12.
Front Plant Sci ; 15: 1358974, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38559764

RESUMO

Sexual reproduction of Zygnematophyceae by conjugation is a less investigated topic due to the difficulties of the induction of this process and zygospore ripening under laboratory conditions. For this study, we collected field sampled zygospores of Spirogyra mirabilis and three additional Spirogyra strains in Austria and Greece. Serial block-face scanning electron microscopy was performed on high pressure frozen and freeze substituted zygospores and 3D reconstructions were generated, allowing a comprehensive insight into the process of zygospore maturation, involving storage compound and organelle rearrangements. Chloroplasts are drastically changed, while young stages contain both parental chloroplasts, the male chloroplasts are aborted and reorganised as 'secondary vacuoles' which initially contain plastoglobules and remnants of thylakoid membranes. The originally large pyrenoids and the volume of starch granules is significantly reduced during maturation (young: 8 ± 5 µm³, mature: 0.2 ± 0.2 µm³). In contrast, lipid droplets (LDs) increase significantly in number upon zygospore maturation, while simultaneously getting smaller (young: 21 ± 18 µm³, mature: 0.1 ± 0.2 and 0.5 ± 0.9 µm³). Only in S. mirabilis the LD volume increases (34 ± 29 µm³), occupying ~50% of the zygospore volume. Mature zygospores contain barite crystals as confirmed by Raman spectroscopy with a size of 0.02 - 0.05 µm³. The initially thin zygospore cell wall (~0.5 µm endospore, ~0.8 µm exospore) increases in thickness and develops a distinct, electron dense mesospore, which has a reticulate appearance (~1.4 µm) in Spirogyra sp. from Greece. The exo- and endospore show cellulose microfibrils in a helicoidal pattern. In the denser endospore, pitch angles of the microfibril layers were calculated: ~18 ± 3° in S. mirabilis, ~20 ± 3° in Spirogyra sp. from Austria and ~38 ± 8° in Spirogyra sp. from Greece. Overall this study gives new insights into Spirogyra sp. zygospore development, crucial for survival during dry periods and dispersal of this genus.

13.
Cureus ; 16(3): e56948, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38665719

RESUMO

Our purpose is to report a patient with a novel variant in the fibrillin-1 (FBN1) gene causing the Marfan syndrome (MFS). The 29-year-old female patient with musculoskeletal, cardiovascular, and ocular findings compatible with the MFS had a novel pathogenic mutation on the FBN1 gene. We report on a patient whose clinical findings are compatible with the MFS. This patient's variant on the FBN1 gene leading to the syndrome has not been previously described. Additional investigations are needed to determine whether this variant contributes to the development of camptodactyly in patients with the syndrome.

14.
Elife ; 132024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639993

RESUMO

In the Firmicutes phylum, GpsB is a membrane associated protein that coordinates peptidoglycan synthesis with cell growth and division. Although GpsB has been studied in several bacteria, the structure, function, and interactome of Staphylococcus aureus GpsB is largely uncharacterized. To address this knowledge gap, we solved the crystal structure of the N-terminal domain of S. aureus GpsB, which adopts an atypical, asymmetric dimer, and demonstrates major conformational flexibility that can be mapped to a hinge region formed by a three-residue insertion exclusive to Staphylococci. When this three-residue insertion is excised, its thermal stability increases, and the mutant no longer produces a previously reported lethal phenotype when overexpressed in Bacillus subtilis. In S. aureus, we show that these hinge mutants are less functional and speculate that the conformational flexibility imparted by the hinge region may serve as a dynamic switch to fine-tune the function of the GpsB complex and/or to promote interaction with its various partners. Furthermore, we provide the first biochemical, biophysical, and crystallographic evidence that the N-terminal domain of GpsB binds not only PBP4, but also FtsZ, through a conserved recognition motif located on their C-termini, thus coupling peptidoglycan synthesis to cell division. Taken together, the unique structure of S. aureus GpsB and its direct interaction with FtsZ/PBP4 provide deeper insight into the central role of GpsB in S. aureus cell division.


Assuntos
Proteínas de Bactérias , Proteínas do Citoesqueleto , Ligação Proteica , Conformação Proteica , Staphylococcus aureus , Staphylococcus aureus/metabolismo , Staphylococcus aureus/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Proteínas do Citoesqueleto/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/química , Cristalografia por Raios X , Proteínas de Ligação às Penicilinas/metabolismo , Proteínas de Ligação às Penicilinas/genética , Proteínas de Ligação às Penicilinas/química , Modelos Moleculares
15.
Biol Chem ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38666334

RESUMO

T-cell therapy has emerged as an effective approach for treating viral infections and cancers. However, a significant challenge is the selection of T-cell receptors (TCRs) that exhibit the desired functionality. Conventionally in vitro techniques, such as peptide sensitivity measurements and cytotoxicity assays, provide valuable insights into TCR potency but are labor-intensive. In contrast, measuring ligand binding properties (z-Movi technology) could provide an accelerated processing while showing robust correlations with T-cell functions. In this study, we assessed whether cell avidity can predict functionality also in the context of TCR-engineered T cells. To this end, we developed a flexible system for TCR re-expression by generating a Jurkat-derived T cell clone lacking TCR and CD3 expression through CRISPR-Cas9-mediated TRBC knockout. The knockin of a transgenic TCR into the TRAC locus restored TCR/CD3 expression, allowing for CD3-based purification of TCR-engineered T cells. Subsequently, we characterized these engineered cell lines by functional readouts, and assessment of binding properties through the z-Movi technology. Our findings revealed a strong correlation between the cell avidities and functional sensitivities of Jurkat TCR-T cells. Altogether, by integrating cell avidity measurements with our versatile T cell engineering platform, we established an accelerated system for enhancing the in vitro selection of clinically relevant TCRs.

16.
Eur J Neurol ; : e16304, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38666798

RESUMO

BACKGROUND AND PURPOSE: Logopenic variant primary progressive aphasia (lvPPA) is a major variant presentation of Alzheimer's disease (AD) that signals the importance of communication dysfunction across AD phenotypes. A clinical staging system is lacking for the evolution of AD-associated communication difficulties that could guide diagnosis and care planning. Our aim was to create a symptom-based staging scheme for lvPPA, identifying functional milestones relevant to the broader AD spectrum. METHODS: An international lvPPA caregiver cohort was surveyed on symptom development under an 'exploratory' survey (34 UK caregivers). Feedback from this survey informed the development of a 'consolidation' survey (27 UK, 10 Australian caregivers) in which caregivers were presented with six provisional clinical stages and feedback was analysed using a mixed-methods approach. RESULTS: Six clinical stages were endorsed. Early symptoms included word-finding difficulty, with loss of message comprehension and speech intelligibility signalling later-stage progression. Additionally, problems with hearing in noise, memory and route-finding were prominent early non-verbal symptoms. 'Milestone' symptoms were identified that anticipate daily-life functional transitions and care needs. CONCLUSIONS: This work introduces a new symptom-based staging scheme for lvPPA, and highlights milestone symptoms that could inform future clinical scales for anticipating and managing communication dysfunction across the AD spectrum.

17.
PLoS One ; 19(4): e0301599, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38557681

RESUMO

In this study, structural images of 1048 healthy subjects from the Human Connectome Project Young Adult study and 94 from ADNI-3 study were processed by an in-house tractography pipeline and analyzed together with pre-processed data of the same subjects from braingraph.org. Whole brain structural connectome features were used to build a simple correlation-based regression machine learning model to predict intelligence and age of healthy subjects. Our results showed that different forms of intelligence as well as age are predictable to a certain degree from diffusion tensor imaging detecting anatomical fiber tracts in the living human brain. Though we did not identify significant differences in the prediction capability for the investigated features depending on the imaging feature extraction method, we did find that crystallized intelligence was consistently better predictable than fluid intelligence from structural connectivity data through all datasets. Our findings suggest a practical and scalable processing and analysis framework to explore broader research topics employing brain MR imaging.


Assuntos
Conectoma , Imagem de Tensor de Difusão , Adulto Jovem , Humanos , Imagem de Tensor de Difusão/métodos , Conectoma/métodos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Inteligência
18.
Inorg Chem ; 63(18): 8502-8509, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38657029

RESUMO

Nitridophosphates and nitridogermanates attract high interest in current research due to their structural versatility. Herein, the elastic properties of GeP2N4 were investigated by single-crystal X-ray diffraction (XRD) upon compression to 44.4(1) GPa in a diamond anvil cell. Its isothermal bulk modulus was determined to be 82(6) GPa. At 44.4(1) GPa, laser heating resulted in the formation of multiple crystalline phases, one of which was identified as unprecedented germanium nitridophosphate GePN3. Its structure was elucidated from single-crystal XRD data (C2/c (no. 15), a = 8.666(5), b = 8.076(4), c = 4.691(2) Å, ß = 101.00(7)°) and is built up from layers of GeN6 octahedra and PN4 tetrahedra. The GeN6 octahedra form double zigzag chains, while the PN4 tetrahedra are found in single zigzag chains. GePN3 can be recovered to ambient conditions with a unit cell volume increase of about 12%. It combines PV and GeIV in a condensed nitridic network for the first time.

19.
J Chromatogr A ; 1720: 464810, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38471299

RESUMO

Nowadays, the higher peak capacity achievable by comprehensive two-dimensional liquid chromatography (LC×LC) for the analysis of vegetal samples is well-recognized. In addition, numerous compounds may be present in very different amounts. Cannabinoids and terpenes represent the main components of Cannabis sativa inflorescence samples, whose quantities are relevant for many application purposes. The analyses of both families are performed by different methods, at least two different separation methodologies, mainly according to their chemical characteristics and concentration levels. In this work, concentration differences and sample complexity issues were addressed using an LC×LC method that incorporates an optimized modulation strategy, namely smart active modulation, for the simultaneous analysis of cannabinoids and terpenes. The system was built by interposing an active flow splitter pump between both dimensions. This set up aimed to exploit the known advantages of LC×LC. In addition, here we proposed to use the splitter pump for online control over the splitting ratio to facilitate the selective dilution of different eluted fractions containing compounds with highly different concentrations. This work represents the first application and demonstration of smart active modulation (SAM) in LC×LC to simultaneously determine analytes with significant differences in concentration levels present in complex samples. The proposed method was tested with eight different strains, from which fingerprints were taken, and numerous cannabinoids and terpenes were identified in these samples. With this strategy, between 49 and 54 peaks were obtained in the LC×LC chromatograms corresponding to different strains. THCA-A was the main component in six strains, while CBDA was the main component in the other two strains. The main terpenes found were myrcene (in five strains), limonene (in two strains), and humulene (in one strain). Additionally, numerous other cannabinoids and terpenes were identified in these samples, providing valuable compositional information for growers, as well as medical and recreational users. The SAM strategy here proposed is simple and it can be extended to other complex matrices.


Assuntos
Canabinoides , Cannabis , Humanos , Canabinoides/análise , Cannabis/química , Terpenos/análise , Inflorescência/química , Cromatografia Gasosa-Espectrometria de Massas , Cromatografia Líquida de Alta Pressão
20.
Eur J Intern Med ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38555253

RESUMO

BACKGROUND: Acute myocardial infarction is associated with the release of the co-transmitter neuropeptide-Y (NPY). NPY acts as a potent vasoconstrictor and is associated with microvascular dysfunction after ST-elevation myocardial infarction (STEMI). This study comprehensively evaluated the association of plasma NPY with myocardial function and infarct severity, visualized by cardiac magnetic resonance (CMR) imaging, in STEMI patients revascularized by primary percutaneous coronary intervention (PCI). METHODS: In this observational study, we included 260 STEMI patients enrolled in the prospective MARINA-STEMI (NCT04113356) study. Plasma NPY concentrations were measured by an immunoassay 24h after PCI from peripheral venous blood samples. Left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), infarct size (IS) and microvascular obstruction (MVO) were determined using CMR imaging. RESULTS: Median plasma concentrations of NPY were 70 [interquartile range (IQR):35-115] pg/ml. NPY levels above median were significantly associated with lower LVEF (48%vs.52%, p=0.004), decreased GLS (-8.8%vs.-12.6%, p<0.001) and larger IS (17%vs.13%, p=0.041) in the acute phase after infarction as well as after 4 months (LVEF:50%vs.52%, p=0.030, GLS:-10.5vs.-12.9,p<0.001,IS:13%vs.10%,p=0.011). In addition, NPY levels were significantly related to presence of MVO (58%vs.52%, p=0.041). Moreover, in multivariable linear regression analysis, NPY remained significantly associated with all investigated CMR parameters (LVEF:p<0.001,GLS:p<0.001,IS:p=0.003,MVO:p=0.042) independent of other established clinical variables including high-sensitivity cardiac troponin T, pre-interventional TIMI flow 0 and left anterior descending artery as culprit lesion location. CONCLUSION: High plasma levels of NPY, measured 24h after STEMI, were independently associated with lower LVEF, decreased GLS, larger IS as well as presence of MVO, indicating plasma NPY as a novel clinical risk marker post STEMI.

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