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1.
Chem Commun (Camb) ; 60(56): 7148-7151, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38860653

RESUMO

We report the use of DOTA as a chelator for titanium. The resulting complex is fully characterised and in vitro stability studies reveal its high kinetic inertness against transmetallation and transchelation. The radiolabeling of DOTA with 45Ti, via a guaiacol-based liquid-liquid extraction method, leads to a high radiochemical conversion up to 98%.


Assuntos
Compostos Heterocíclicos com 1 Anel , Compostos Radiofarmacêuticos , Titânio , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/síntese química , Compostos Heterocíclicos com 1 Anel/química , Compostos Heterocíclicos com 1 Anel/síntese química , Titânio/química , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Compostos Aza/química , Compostos Aza/síntese química , Quelantes/química , Quelantes/síntese química , Estrutura Molecular
2.
FASEB J ; 38(9): e23641, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38690717

RESUMO

Cholinergic urticaria is a dermatological disease characterized by the presence of large patches of red skin and transient hives triggered by factors, such as exercise, sweating, and psychological tension. This skin problem is hypothesized to be attributed to a reduced expression of acetylcholinesterase (AChE), an enzyme responsible for hydrolyzing acetylcholine (ACh). Consequently, ACh is thought to the leak from sympathetic nerves to skin epidermis. The redundant ACh stimulates the mast cells to release histamine, triggering immune responses in skin. Here, the exposure of ultraviolet B in skin suppressed the expression of AChE in keratinocytes, both in in vivo and in vitro models. The decrease of the enzyme was resulted from a declined transcription of ACHE gene mediated by micro-RNAs, that is, miR-132 and miR-212. The levels of miR-132 and miR-212 were markedly induced by exposure to ultraviolet B, which subsequently suppressed the transcriptional rate of ACHE. In the presence of low level of AChE, the overflow ACh caused the pro-inflammatory responses in skin epidermis, including increased secretion of cytokines and COX-2. These findings suggest that ultraviolet B exposure is one of the factors contributing to cholinergic urticaria in skin.


Assuntos
Acetilcolinesterase , Queratinócitos , MicroRNAs , Pele , Raios Ultravioleta , Urticária , Acetilcolinesterase/metabolismo , Acetilcolinesterase/genética , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Animais , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Pele/efeitos da radiação , Pele/metabolismo , Urticária/metabolismo , Urticária/etiologia , Camundongos , Acetilcolina/metabolismo , Masculino
3.
ACS Appl Mater Interfaces ; 16(15): 19672-19680, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38576132

RESUMO

Traditional multilayer antireflection (AR) surfaces are of significant importance for numerous applications, such as laser optics, camera lenses, and eyeglasses. Recently, technological advances in the fabrication of biomimetic AR surfaces capable of delivering broadband omnidirectional high transparency combined with self-cleaning properties have opened an alternative route toward realization of multifunctional surfaces which would be beneficial for touchscreen displays or solar harvesting devices. However, achieving the desired surface properties often requires sophisticated lithography fabrication methods consisting of multiple steps. In the present work, we show the design and implementation of mechanically robust AR surfaces fabricated by a lithography-free process using thermally dewetted silver as an etching mask. Both-sided nanohole (NH) surfaces exhibit transmittance above 99% in the visible or the near-infrared ranges combined with improved angular response at an angle of incidence of up to θi = 60°. Additionally, the NHs demonstrate excellent mechanical resilience against repeated abrasion with cheesecloth due to favorable redistribution of the shearing mechanical forces, making them a viable option for touchscreen display applications.

4.
Biochemistry ; 63(10): 1246-1256, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38662574

RESUMO

Guanylate cyclase activating protein-5 (GCAP5) in zebrafish photoreceptors promotes the activation of membrane receptor retinal guanylate cyclase (GC-E). Previously, we showed the R22A mutation in GCAP5 (GCAP5R22A) abolishes dimerization of GCAP5 and activates GC-E by more than 3-fold compared to that of wild-type GCAP5 (GCAP5WT). Here, we present ITC, NMR, and functional analysis of GCAP5R22A to understand how R22A causes a decreased dimerization affinity and increased cyclase activation. ITC experiments reveal GCAP5R22A binds a total of 3 Ca2+, including two sites in the nanomolar range followed by a single micromolar site. The two nanomolar sites in GCAP5WT were not detected by ITC, suggesting that R22A may affect the binding of Ca2+ to these sites. The NMR-derived structure of GCAP5R22A is overall similar to that of GCAP5WT (RMSD = 2.3 Å), except for local differences near R22A (Q19, W20, Y21, and K23) and an altered orientation of the C-terminal helix near the N-terminal myristate. GCAP5R22A lacks an intermolecular salt bridge between R22 and D71 that may explain the weakened dimerization. We present a structural model of GCAP5 bound to GC-E in which the R22 side-chain contacts exposed hydrophobic residues in GC-E. Cyclase assays suggest that GC-E binds to GCAP5R22A with ∼25% higher affinity compared to GCAP5WT, consistent with more favorable hydrophobic contact by R22A that may help explain the increased cyclase activation.


Assuntos
Proteínas Ativadoras de Guanilato Ciclase , Guanilato Ciclase , Peixe-Zebra , Proteínas Ativadoras de Guanilato Ciclase/metabolismo , Proteínas Ativadoras de Guanilato Ciclase/genética , Proteínas Ativadoras de Guanilato Ciclase/química , Animais , Guanilato Ciclase/genética , Guanilato Ciclase/metabolismo , Guanilato Ciclase/química , Peixe-Zebra/metabolismo , Multimerização Proteica , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/química , Proteínas de Peixe-Zebra/metabolismo , Cálcio/metabolismo , Modelos Moleculares , Ativação Enzimática , Ressonância Magnética Nuclear Biomolecular , Mutação , Conformação Proteica , Retina/metabolismo
5.
iScience ; 27(4): 109415, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38523789

RESUMO

Brain organoids derived from human pluripotent stem cells are a promising tool for studying human neurodevelopment and related disorders. Here, we generated long-term cultures of cortical brain organoid slices (cBOS) grown at the air-liquid interphase from regionalized cortical organoids. We show that cBOS host mature neurons and astrocytes organized in complex architecture. Whole-cell patch-clamp demonstrated subthreshold synaptic inputs and action potential firing of neurons. Spontaneous intracellular calcium signals turned into synchronous large-scale oscillations upon combined disinhibition of NMDA receptors and blocking of GABAA receptors. Brief metabolic inhibition to mimic transient energy restriction in the ischemic brain induced reversible intracellular calcium loading of cBOS. Moreover, metabolic inhibition induced a reversible decline in neuronal ATP as revealed by ATeam1.03YEMK. Overall, cBOS provide a powerful platform to assess morphological and functional aspects of human neural cells in intact minimal networks and to address the pathways that drive cellular damage during brain ischemia.

6.
Adv Ther ; 41(5): 2010-2027, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38554238

RESUMO

INTRODUCTION: For some immune-mediated disorders, despite the range of therapies available there is limited evidence on which treatment sequences are best for patients and healthcare systems. We investigated how their selection can impact outcomes in an Italian setting. METHODS: A 3-year state-transition treatment-sequencing model calculated potential effectiveness improvements and budget reallocation considerations associated with implementing optimal sequences in ankylosing spondylitis (AS), Crohn's disease (CD), non-radiographic axial spondyloarthritis (NR-AxSpA), plaque psoriasis (PsO), psoriatic arthritis (PsA), rheumatoid arthritis (RA), and ulcerative colitis (UC). Sequences included three biological or disease-modifying treatments, followed by best supportive care. Disease-specific response measures were selected on the basis of clinical relevance, data availability, and data quality. Efficacy was differentiated between biologic-naïve and experienced populations, where possible, using published network meta-analyses and real-world data. All possible treatment sequences, based on reimbursement as of December 2022 in Italy (analyses' base country), were simulated. RESULTS: Sequences with the best outcomes consistently employed the most efficacious therapies earlier in the treatment pathway. Improvements to prescribing practice are possible in all diseases; however, most notable was UC, where the per-patient 3-year average treatment failure was 37.3% higher than optimal. The results focused on the three most crowded and prevalent immunological sub-condition diseases in dermatology, rheumatology, and gastroenterology: PsO, RA, and UC, respectively. By prescribing from within the top 20% of the most efficacious sequences, the model found a 15.1% reduction in treatment failures, with a 1.59% increase in drug costs. CONCLUSIONS: Prescribing more efficacious treatments earlier provides a greater opportunity to improve patient outcomes and minimizes treatment failures.


Assuntos
Artrite Psoriásica , Humanos , Itália , Artrite Psoriásica/tratamento farmacológico , Psoríase/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Espondilite Anquilosante/tratamento farmacológico , Resultado do Tratamento , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Antirreumáticos/uso terapêutico
7.
J Environ Qual ; 53(2): 232-240, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38348512

RESUMO

Saturated buffers are a newly developed agricultural best management practice used to redirect tile flow away from waterways, thereby mitigating nutrient losses and downstream eutrophication. This study evaluated the potential benefits of a novel saturated buffer design, which included pitchfork-shaped (PF) dispersion lines and a backflow check valve, that was installed alongside a traditional or standard (ST) buffer on a field in Moultrie County, Illinois, in the spring of 2019. Daily flow measurements and routine water samples were used to monitor the movement of water through both buffers and estimate nutrient loads. During observation days in 2020 and 2021, the PF buffer diverted 35% and 1.9% of incoming tile flow, respectively, while the ST buffer increased effluent rates by 116% and 137% over the same period. Both the PF and ST buffers experienced backflow from 30% to 47% of the monitoring period, well above the often reported 5%. Ultimately, the efficacy of saturated buffers could be improved with minimal, low-cost additions to their designs. Check valves are a simple supplement to saturated buffer design that can enhance flow diversion and potential nutrient removal. Added dispersion lines provide more opportunity for diversion of tile flow; however, they require more land to be removed from agricultural production and could increase backflow volumes, so the costs and benefits should be weighed.


Assuntos
Agricultura , Eutrofização , Illinois , Estações do Ano , Água
8.
Inorg Chem ; 63(21): 9624-9637, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38407062

RESUMO

Homoleptic tetramethylaluminates Ln(AlMe4)3 react with KTptBu,Me (TptBu,Me = tris(3-tBu-5-Me-pyrazolyl)borato) to yield rare-earth-metal methylidene complexes (TptBu,Me)Ln(µ3-CH2)[(µ-Me)AlMe2]2 (Ln = La, Ce, Nd). The lanthanum reaction is prone to additional C-H- and B-N-bond activation, affording coproducts La[HB(pzMe,tBu)(pzCMe2,Me)2][(µ-CH2)(µ-Me)AlMe2]2 and [La(µ-pztBu,Me)(AlMe4)2]2 (pztBu,Me = 3-tBu-5-Me-pyrazolato). The protonolysis reaction of Ln(AlMe4)3 and HpztBu,Me provides more efficient access to [Ln(µ-pztBu,Me)(AlMe4)2]2 (Ln = La, Nd). Treatment of Ln(AlMe4)3 with KTpMe,Me led to methylidene complexes (TpMe,Me)Ln(µ3-CH2)[(µ-Me)AlMe2]2 (Ln = Nd, Sm) or bis(tetramethylaluminate) complexes (TpMe,Me)Ln(AlMe4)2 (Ln = Y, Lu). The neodymium reaction generated methine derivative (TpMe,Me)Nd[(µ4-CH)(AlMe2)2(µ-pz,Me,Me)][(µ-Me)AlMe2] as a minor coproduct. The reaction of Ln(GaMe4)3 (Ln = Y, La, Ce, Nd, Sm, Ho) with HTptBu,Me gave methylidene complexes (TptBu,Me)Ln(µ3-CH2)[(µ-Me)GaMe2]2 (Ln = La, Ce, Nd, Sm) and alkyl complexes (TptBu,Me)LnMe[(µ-Me)GaMe3] (Ln = Y, Ho), while competing B-N bond activation reactions produced GaMe2[BH(Me)(µ-pztBu,Me)2] and (TptBu,Me)Ln(η2-pztBu,Me)[(µ-Me)GaMe3] (Ln = Y, Ho). The steric impact of the TpR,Me ligands was examined by cone angle calculations. Rare-earth-metal methylidene complexes (TptBu,Me)Ln(µ3-CH2)[(µ-Me)EMe2]2 (E = Al, Ga) successfully promote carbonyl methylenation reactions upon addition of ketone.

9.
Chempluschem ; 89(5): e202300731, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38252804

RESUMO

Zwitterions (ZIs), which are molecules bearing an equal number of positive and negative charges and typically possessing large dipole moments, can play an important role in improving the characteristics of a wide variety of novel battery electrolytes. Significant Coulombic interactions among ZI charged groups and any mobile ions present can lead to several beneficial phenomena within electrolytes, such as increased salt dissociation, the formation of ordered pathways for ion transport, and enhanced mechanical robustness. In some cases, ZI additives can also boost electrochemical stability at the electrolyte/electrode interface and enable longer battery cycling. Here, a brief summary of selected key historical and recent advances in the use of ZI materials to enrich the performance of three distinct classes of battery electrolytes is presented. These include: ionic liquid-based, conventional solvent-based, and solid matrix-based (non-ceramic) electrolytes. Exploring a greater chemical diversity of ZI types and electrolyte pairings will likely lead to more discoveries that can empower next-generation battery designs in the years to come.

10.
Chem Mater ; 35(22): 9623-9631, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38047185

RESUMO

Currently only Eu2+-based scintillators have approached the light yield needed to improve the 2% energy resolution at 662 keV of LaBr3:Ce3+,Sr2+. Their major limitation, however, is the significant self-absorption due to Eu2+. CsCu2I3 is an interesting new small band gap scintillator. It is nonhygroscopic and nontoxic, melts congruently, and has an extremely low afterglow, a density of 5.01 g/cm3, and an effective atomic number of 50.6. It shows self-trapped exciton emission at room temperature. The large Stokes shift of this emission ensures that this material is not sensitive to self-absorption, tackling one of the major problems of Eu2+-based scintillators. An avalanche photo diode, whose optimal detection efficiency matches the 570 nm mean emission wavelength of CsCu2I3, was used to measure pulse height spectra. From the latter, a light yield of 36 000 photons/MeV and energy resolution of 4.82% were obtained. The scintillation proportionality of CsCu2I3 was found to be on par with that of SrI2:Eu2+. Based on temperature-dependent emission and decay measurements, it was demonstrated that CsCu2I3 emission is already about 50% quenched at room temperature. Using temperature-dependent pulse height measurements, it is shown that the light yield can be increased up to 60 000 photons/MeV by cooling to 200 K, experimentally demonstrating the scintillation potential of CsCu2I3. Below this temperature, the light yield starts to decrease, which can be linked to the unusually large increase in the band gap energy of CsCu2I3.

11.
Nature ; 623(7989): 1070-1078, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37968394

RESUMO

Three billion years of evolution has produced a tremendous diversity of protein molecules1, but the full potential of proteins is likely to be much greater. Accessing this potential has been challenging for both computation and experiments because the space of possible protein molecules is much larger than the space of those likely to have functions. Here we introduce Chroma, a generative model for proteins and protein complexes that can directly sample novel protein structures and sequences, and that can be conditioned to steer the generative process towards desired properties and functions. To enable this, we introduce a diffusion process that respects the conformational statistics of polymer ensembles, an efficient neural architecture for molecular systems that enables long-range reasoning with sub-quadratic scaling, layers for efficiently synthesizing three-dimensional structures of proteins from predicted inter-residue geometries and a general low-temperature sampling algorithm for diffusion models. Chroma achieves protein design as Bayesian inference under external constraints, which can involve symmetries, substructure, shape, semantics and even natural-language prompts. The experimental characterization of 310 proteins shows that sampling from Chroma results in proteins that are highly expressed, fold and have favourable biophysical properties. The crystal structures of two designed proteins exhibit atomistic agreement with Chroma samples (a backbone root-mean-square deviation of around 1.0 Å). With this unified approach to protein design, we hope to accelerate the programming of protein matter to benefit human health, materials science and synthetic biology.


Assuntos
Algoritmos , Simulação por Computador , Conformação Proteica , Proteínas , Humanos , Teorema de Bayes , Evolução Molecular Direcionada , Aprendizado de Máquina , Modelos Moleculares , Dobramento de Proteína , Proteínas/química , Proteínas/metabolismo , Semântica , Biologia Sintética/métodos , Biologia Sintética/tendências
13.
Leukemia ; 37(12): 2448-2456, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37798328

RESUMO

T-cell malignancies are associated with frequent relapse and high morbidity, which is partly due to the lack of effective or targeted treatment options. To broaden the use of CAR-T cells in pan T-cell malignancies, we developed an allogeneic "universal" CD2-targeting CAR-T cell (UCART2), in which the CD2 antigen is deleted to prevent fratricide, and the T-cell receptor is removed to prevent GvHD. UCART2 demonstrated efficacy against T-ALL and CTCL and prolonged the survival of tumor-engrafted NSG mice in vivo. To evaluate the impact of CD2 on CAR-T function, we generated CD19 CAR-T cells (UCART19) with or without CD2 deletion, single-cell secretome analysis revealed that CD2 deletion in UCART19 reduced frequencies of the effector cytokines (Granzyme-B and IFN-γ). We also observed that UCART19ΔCD2 had reduced anti-tumor efficacy compared to UCART19 in a CD19+NALM6 xenograft model. Of note is that the reduced efficacy resulting from CD2 deletion was reversed when combined with rhIL-7-hyFc, a long-acting recombinant human interleukin-7. Treatment with rhIL-7-hyFc prolonged UCART2 persistence and increased survival in both the tumor re-challenge model and primary patient T-ALL model in vivo. Together, these data suggest that allogeneic fratricide-resistant UCART2, in combination with rhIL-7-hyFc, could be a suitable approach for treating T-cell malignancies.


Assuntos
Leucemia-Linfoma Linfoblástico de Células T Precursoras , Receptores de Antígenos Quiméricos , Humanos , Camundongos , Animais , Linfócitos T , Receptores de Antígenos Quiméricos/genética , Recidiva Local de Neoplasia , Imunoterapia Adotiva/métodos , Receptores de Antígenos de Linfócitos T , Antígenos CD19
14.
BMC Zool ; 8(1): 22, 2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37723576

RESUMO

This study investigated the reproductive traits of the hermaphroditic four-finger threadfin, Eleutheronema tetradactylum, along the coasts of Thailand during January to December 2021. Fish samples were collected from Pattani Bay, Thailand to assess the sex ratio, gonadosomatic index (GSI), maturity stage and fecundity. Additional fish samples were also collected from other areas to evaluate the length and weight at first sex change (Ls50 and Ws50) and length at first maturity (Lm50). The overall sex ratio for male and female was 1:0.69 with male being predominant throughout the year. Threadfin fish spawn the whole year round with peaks during moderate rainy and heavy rainy seasons. Histological examination confirmed its protandrous hermaphrodite posing multiple spawning habits. The average fecundity was 1.85 × 105 ± 1.05 × 105 eggs and positively related with standard length, body weight, gonad weight, and egg diameter (p < 0.05). The Ls50 and Ws50 were 27.58 cm and 419.39 g, and 29.71 cm and 457.28 g, for fish from Pattani Bay and Samut Prakan province, respectively. The Lm50 of male from Pattani Bay and Samut Prakan province were 25.78 cm and 25.56 cm, respectively, which were larger than those from Satun and Nakhon Sri Thammarat provinces. The Lm50 of females from Pattani Bay was smaller than that from Samut Prakan province. This study provided fundamental information on the reproductive characteristics of E. tetradactylum, which can be implemented to support management of natural fish stock and aquaculture development.

15.
Sensors (Basel) ; 23(17)2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37687804

RESUMO

The safety of flight operations depends on the cognitive abilities of pilots. In recent years, there has been growing concern about potential accidents caused by the declining mental states of pilots. We have developed a novel multimodal approach for mental state detection in pilots using electroencephalography (EEG) signals. Our approach includes an advanced automated preprocessing pipeline to remove artefacts from the EEG data, a feature extraction method based on Riemannian geometry analysis of the cleaned EEG data, and a hybrid ensemble learning technique that combines the results of several machine learning classifiers. The proposed approach provides improved accuracy compared to existing methods, achieving an accuracy of 86% when tested on cleaned EEG data. The EEG dataset was collected from 18 pilots who participated in flight experiments and publicly released at NASA's open portal. This study presents a reliable and efficient solution for detecting mental states in pilots and highlights the potential of EEG signals and ensemble learning algorithms in developing cognitive cockpit systems. The use of an automated preprocessing pipeline, feature extraction method based on Riemannian geometry analysis, and hybrid ensemble learning technique set this work apart from previous efforts in the field and demonstrates the innovative nature of the proposed approach.


Assuntos
Algoritmos , Artefatos , Cognição , Eletroencefalografia , Aprendizado de Máquina
16.
Crit Care Explor ; 5(8): e0955, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37614801

RESUMO

OBJECTIVES: Clinical sepsis phenotypes may be defined by a wide range of characteristics such as site of infection, organ dysfunction patterns, laboratory values, and demographics. There is a paucity of literature regarding the impact of site of infection on the timing and pattern of clinical sepsis markers. This study hypothesizes that important phenotypic variation in clinical markers and outcomes of sepsis exists when stratified by infection site. DESIGN: Retrospective cohort study. SETTING: Five hospitals within the Wake Forest Health System from June 2019 to December 2019. PATIENTS: Six thousand seven hundred fifty-three hospitalized adults with a discharge International Classification of Diseases, 10th Revision code for acute infection who met systemic inflammatory response syndrome (SIRS), quick Sepsis-related Organ Failure Assessment (qSOFA), or Sequential Organ Failure Assessment (SOFA) criteria during the index hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome of interest was a composite of 30-day mortality or shock. Infection site was determined by a two-reviewer process. Significant demographic, vital sign, and laboratory result differences were seen across all infection sites. For the composite outcome of shock or 30-day mortality, unknown or unspecified infections had the highest proportion (21.34%) and CNS infections had the lowest proportion (8.11%). Respiratory, vascular, and unknown or unspecified infection sites showed a significantly increased adjusted and unadjusted odds of the composite outcome as compared with the other infection sites except CNS. Hospital time prior to SIRS positivity was shortest in unknown or unspecified infections at a median of 0.88 hours (interquartile range [IQR], 0.22-5.05 hr), and hospital time prior to qSOFA and SOFA positivity was shortest in respiratory infections at a median of 54.83 hours (IQR, 9.55-104.67 hr) and 1.88 hours (IQR, 0.47-17.40 hr), respectively. CONCLUSIONS: Phenotypic variation in illness severity and mortality exists when stratified by infection site. There is a significantly higher adjusted and unadjusted odds of the composite outcome of 30-day mortality or shock in respiratory, vascular, and unknown or unspecified infections as compared with other sites.

17.
JAMA Netw Open ; 6(8): e2329729, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37624600

RESUMO

Importance: The Sepsis Prediction Model (SPM) is a proprietary decision support tool created by Epic Systems; it generates a predicting sepsis score (PSS). The model has not undergone validation against existing sepsis prediction tools, such as Systemic Inflammatory Response Syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), or quick Sepsis-Related Organ Failure Asessement (qSOFA). Objective: To assess the validity and timeliness of the SPM compared with SIRS, qSOFA, and SOFA. Design, Setting, and Participants: This retrospective cohort study included all adults admitted to 5 acute care hospitals in a single US health system between June 5, 2019, and December 31, 2020. Data analysis was conducted from March 2021 to February 2023. Main Outcomes and Measures: A sepsis event was defined as receipt of 4 or more days of antimicrobials, blood cultures collected within ±48 hours of initial antimicrobial, and at least 1 organ dysfunction as defined by the organ dysfunction criteria optimized for the electronic health record (eSOFA). Time zero was defined as 15 minutes prior to qualifying antimicrobial or blood culture order. Results: Of 60 507 total admissions, 1663 (2.7%) met sepsis criteria, with 1324 electronic health record-confirmed sepsis (699 [52.8%] male patients; 298 [22.5%] Black patients; 46 [3.5%] Hispanic/Latinx patients; 945 [71.4%] White patients), 339 COVID-19 sepsis (183 [54.0%] male patients; 98 [28.9%] Black patients; 36 [10.6%] Hispanic/Latinx patients; and 189 [55.8%] White patients), and 58 844 (97.3%; 26 632 [45.2%] male patients; 12 698 [21.6%] Black patients; 3367 [5.7%] Hispanic/Latinx patients; 40 491 White patients) did not meet sepsis criteria. The median (IQR) age was 63 (51 to 73) years for electronic health record-confirmed sepsis, 69 (60 to 77) years for COVID-19 sepsis, and 60 (42 to 72) years for nonsepsis admissions. Within the vendor recommended threshold PSS range of 5 to 8, PSS of 8 or greater had the highest balanced accuracy for classifying a sepsis admission at 0.79 (95% CI, 0.78 to 0.80). Change in SOFA score of 2 or more had the highest sensitivity, at 0.97 (95% CI, 0.97 to 0.98). At a PSS of 8 or greater, median (IQR) time to score positivity from time zero was 68.00 (6.75 to 605.75) minutes. For SIRS, qSOFA, and SOFA, median (IQR) time to score positivity was 7.00 (-105.00 to 08.00) minutes, 74.00 (-22.25 to 599.25) minutes, and 28.00 (-108.50 to 134.00) minutes, respectively. Conclusions and Relevance: In this cohort study of hospital admissions, balanced accuracy of the SPM outperformed other models at higher threshold PSS; however, application of the SPM in a clinical setting was limited by poor timeliness as a sepsis screening tool as compared to SIRS and SOFA.


Assuntos
COVID-19 , Sepse , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Estudos de Coortes , Insuficiência de Múltiplos Órgãos , Escores de Disfunção Orgânica , Estudos Retrospectivos , COVID-19/diagnóstico , COVID-19/epidemiologia , Sepse/diagnóstico
19.
Chemistry ; 29(59): e202302104, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37421647

RESUMO

We present the synthesis of a new type of an expanded porphyrinoid macrocycle with a saddle-shaped morphology and its complexation of C60 guest molecules. The new macrocycle contains four carbazole and four triazole moieties and can be readily synthesized via a copper-catalyzed click reaction. It shows specific photo-physical properties including fluorescence with a high quantum yield of 60 %. The combination of the saddle-shaped geometry with the expanded π-system allows for host-guest interactions with C60 in a stacked polymer fashion. Evidence for the presence of a host-guest complex is provided both in solution by NMR spectroscopy and in the solid state by X-ray structure analysis.

20.
J Am Coll Health ; : 1-10, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37289962

RESUMO

Objective: Assess university students' SARS-CoV-2 antibody seroprevalence and mitigation behaviors over time. Participants: Randomly selected college students (N = 344) in a predominantly rural Southern state. Methods: Participants provided blood samples and completed self-administered questionnaires at three timepoints over the academic year. Adjusted odds ratios and 95% confidence intervals were estimated from logistic regression analyses. Results: SARS-CoV-2 antibody seroprevalence was 18.2% in September 2020, 13.1% in December, and 45.5% in March 2021 (21% for those with no vaccination history). SARS-CoV-2 antibody seroprevalence was associated with large social gatherings, staying local during the summer break, symptoms of fatigue or rhinitis, Greek affiliation, attending Greek events, employment, and using social media as the primary COVID-19 information source. In March 2021, seroprevalence was associated with receiving at least one dose of a COVID-19 vaccination. Conclusion: SARS-CoV-2 seroprevalence was higher in this population of college students than previous studies. Results can assist leaders in making informed decisions as new variants threaten college campuses.

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