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Avian influenza poses a severe threat to poultry production and global food security, prompting the development of vaccination programs in numerous countries. Modified live virus (MLV) vaccines, with their potential for mass application, offer a distinct advantage over existing options. However, concerns surrounding reversion, recombination, and unintended transmission have hindered the progress of MLV development for avian influenza in poultry. To address these concerns, we engineered reassortment-impaired, non-transmissible, safe, immunogenic, and protective MLVs through the rearrangement of internal gene segments and additional modifications to the surface gene segments HA and NA. The unique peptide marker aspartic acid-arginine-proline-alanine-valine-isoleucine-alanine-asparragine (DRPAVIAN) was incorporated into HA, while NA was modified to encode the chicken interleukin-18 (ckIL18) gene (MLV-H9N2-IL). In vitro, the MLV-H9N2 and MLV-H9N2-IL candidates demonstrated stability and virus titers comparable to the wild-type H9N2 strain. In chickens, the MLV-H9N2 and MLV-H9N2-IL candidates did not transmit via direct contact. Co-infection studies with wild-type virus confirmed that the altered HA and NA segments exhibited fitness disadvantages and did not reassort. Vaccinated chickens showed no clinical signs upon vaccination, all seroconverted, and the inclusion of ckIL18 in the MLV-H9N2-IL vaccine enhanced neutralizing antibody production. A significant decrease in viral loads post-challenge underscored the protective effect of the MLVs. The MLV-H9N2-IL vaccine, administered via drinking water, proved immunogenic in chickens in a dose-dependent manner, generating protective levels of neutralizing antibodies upon aggressive homologous virus challenge. In summary, this study lays the groundwork for safe MLVs against avian influenza suitable for mass vaccination efforts.
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Thermoplastic polyurethane (TPU) doped with multi-walled carbon nanotubes (MWCNTs) at 1, 3, 5, and 7 wt% has been studied. The effect of MWCNTs on thermal, viscoelastic, and electric properties in the TPU matrix was characterized by differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and by impedance spectroscopy. The results show that the thermal, electrical, and viscoelastic properties, such as the glass transition temperature, shifted towards high temperatures. The melting temperature decreased, and the conductivity and the storage modulus increased by 61.5 % and 58.3 %. The previously observed behavior on the films is due to the increase in the mass percentage of carbon nanotubes (CNTs) in the TPU matrix. Also, it can be said that the CNTs were homogeneously dispersed in the TPU matrix, preventing the movement of the polymer chains, and generating channels or connections that increase the conductivity and improve the thermal properties of the material.
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Importance: In the US, hepatocellular carcinoma (HCC) has been the most rapidly increasing cancer since 1980, and metabolic dysfunction-associated steatotic liver disease (MASLD) is expected to soon become the leading cause of HCC. Objective: To develop a prediction model for HCC incidence in a cohort of patients with MASLD. Design, Setting, and Participants: This prognostic study was conducted among patients aged at least 18 years with MASLD, identified using diagnosis of MASLD using International Classification of Diseases, Ninth Revision (ICD-9) or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes; natural language processing of radiology imaging report text, which identified patients who had imaging evidence of MASLD but had not been formally diagnosed; or the Dallas Steatosis Index, a risk equation that identifies individuals likely to have MASLD with good precision. Patients were enrolled from Kaiser Permanente Northern California, an integrated health delivery system with more than 4.6 million members, with study entry between January 2009 and December 2018, and follow-up until HCC development, death, or study termination on September 30, 2021. Statistical analysis was performed during February 2023 and January 2024. Exposure: Data were extracted from the electronic health record and included 18 routinely measured factors associated with MASLD. Main Outcome and Measures: The cohort was split (70:30) into derivation and internal validation sets; extreme gradient boosting was used to model HCC incidence. HCC risk was divided into 3 categories, with the cumulative estimated probability of HCC 0.05% or less classified as low risk; 0.05% to 0.09%, medium risk; and 0.1% or greater, high risk. Results: A total of 1â¯811â¯461 patients (median age [IQR] at baseline, 52 [41-63] years; 982â¯300 [54.2%] female) participated in the study. During a median (range) follow-up of 9.3 (5.8-12.4) years, 946 patients developed HCC, for an incidence rate of 0.065 per 1000 person-years. The model achieved an area under the curve of 0.899 (95% CI, 0.882-0.916) in the validation set. At the medium-risk threshold, the model had a sensitivity of 87.5%, specificity of 81.4%, and a number needed to screen of 406. At the high-risk threshold, the model had a sensitivity of 78.4%, a specificity of 90.1%, and a number needed to screen of 241. Conclusions and Relevance: This prognostic study of more than 1.8 million patients with MASLD used electronic health record data to develop a prediction model to discriminate between individuals with and without incident HCC with good precision. This model could serve as a starting point to identify patients with MASLD who may need intervention and/or HCC surveillance.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiologia , Feminino , Masculino , Neoplasias Hepáticas/epidemiologia , Pessoa de Meia-Idade , Idoso , Incidência , California/epidemiologia , Adulto , Fígado Gorduroso/epidemiologia , Fígado Gorduroso/complicações , Prognóstico , Fatores de Risco , Estudos de CoortesRESUMO
BACKGROUND AND OBJECTIVES: Few population-based studies have assessed associations between the use of antithrombotic (platelet antiaggregant or anticoagulant) drugs and location-specific risks of spontaneous intracerebral hemorrhage (s-ICH). In this study, we estimated associations between antithrombotic drug use and the risk of lobar vs nonlobar incident s-ICH. METHODS: Using Danish nationwide registries, we identified cases in the Southern Denmark Region of first-ever s-ICH in patients aged 50 years or older between 2009 and 2018. Each verified case was classified as lobar or nonlobar s-ICH and matched to controls in the general population by age, sex, and calendar year. Prior antithrombotic use was ascertained from a nationwide prescription registry. We calculated odds ratios (aORs) for associations between the use of clopidogrel, aspirin, direct oral anticoagulants (DOACs) or vitamin K antagonists (VKA), and lobar and nonlobar ICH in conditional logistic regression analyses that were adjusted for potential confounders. RESULTS: A total of 1,040 cases of lobar (47.9% men, mean age [SD] 75.2 [10.7] years) and 1,263 cases of nonlobar s-ICH (54.2% men, mean age 73.6 [11.4] years) were matched to 41,651 and 50,574 controls, respectively. A stronger association with lobar s-ICH was found for clopidogrel (cases: 7.6%, controls: 3.5%; aOR 3.46 [95% CI 2.45-4.89]) vs aspirin (cases: 22.9%, controls: 20.4%; aOR 2.14 [1.74-2.63; p = 0.019). Corresponding estimates for nonlobar s-ICH were not different between clopidogrel (cases: 5.4%, controls: 3.4%; aOR 2.44 [1.71-3.49]) and aspirin (cases: 20.7%, controls: 19.2%; aOR 1.77 [1.47-2.15]; p = 0.12). VKA use was associated with higher odds of both lobar (cases: 14.3%, controls: 6.1%; aOR 3.66 [2.78-4.80]) and nonlobar (cases: 15.4%, controls: 5.5%; aOR 4.62 [3.67-5.82]) s-ICH. The association of DOAC use with lobar s-ICH (cases: 3.5%, controls: 2.7%; aOR 1.66 [1.02-2.70]) was weaker than that of VKA use (p = 0.006). Corresponding estimates for nonlobar s-ICH were not different between DOACs (cases: 5.1%, controls: 2.4%; aOR 3.44 [2.33-5.08]) and VKAs (p = 0.20). DISCUSSION: Antithrombotics were associated with higher risks of s-ICH, but the strength of the associations varied by s-ICH location and drug, which may reflect differences in the cerebral microangiopathies associated with lobar vs nonlobar hemorrhages and the mechanisms of drug action.
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Hemorragia Cerebral , Fibrinolíticos , Sistema de Registros , Humanos , Masculino , Feminino , Idoso , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/induzido quimicamente , Dinamarca/epidemiologia , Pessoa de Meia-Idade , Fibrinolíticos/efeitos adversos , Idoso de 80 Anos ou mais , Inibidores da Agregação Plaquetária/efeitos adversos , Anticoagulantes/efeitos adversos , Clopidogrel/efeitos adversos , Clopidogrel/uso terapêutico , Aspirina/efeitos adversos , IncidênciaRESUMO
Oral contraceptive pills, of all types, are used by approximately 151 million women worldwide; however, a clear understanding of the concentrations of endogenous and exogenous hormones across a 28-day combination monophasic oral contraceptive pill pack is not well described. In our study of 14 female participants taking various combination monophasic oral contraceptive pills, we found significant fluctuations in endogenous and exogenous hormone levels throughout the pill cycle. Our analysis revealed significantly greater levels of ethinyl estradiol on the 20th and 21st days of active pill ingestion, compared with days 1-2 (active) and days 27-28 (inactive pill ingestion). Conversely, estradiol concentrations decreased during active pill consumption, while progestin and progesterone levels remained stable. During the 7 days of inactive pill ingestion, estradiol levels rose sharply and were significantly higher at days 27-28 compared with the mid and late active phase time points, while ethinyl estradiol declined and progestin did not change. These findings challenge the previous assumption that endogenous and exogenous hormones are stable throughout the 28-day pill cycle.NEW & NOTEWORTHY The results from this study have wide-ranging implications for research and treatment in women's health including considerations in research design and interpretation for studies including women taking oral contraceptives, the potential for more precise and personalized methods of dosing to reduce unwanted side effects and adverse events, and the potential treatment of a variety of disorders ranging from musculoskeletal to neurological with exogenous hormones.
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Anticoncepcionais Orais Combinados , Estradiol , Etinilestradiol , Ciclo Menstrual , Progesterona , Espectrometria de Massas em Tandem , Humanos , Feminino , Adulto , Anticoncepcionais Orais Combinados/administração & dosagem , Espectrometria de Massas em Tandem/métodos , Etinilestradiol/administração & dosagem , Etinilestradiol/sangue , Progesterona/sangue , Ciclo Menstrual/efeitos dos fármacos , Ciclo Menstrual/sangue , Adulto Jovem , Estradiol/sangue , Cromatografia Líquida/métodos , Progestinas/sangue , Progestinas/administração & dosagem , Anticoncepcionais Orais Hormonais/administração & dosagemRESUMO
Background: Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2i) and Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) improve cardiorenal outcomes in patients with type 2 diabetes. Equitable use of SGLT2i and GLP-1 RA has the potential to reduce racial and ethnic health disparities. We evaluated trends in pharmacy dispensing of SGLT2i and GLP-1 RA by race and ethnicity. Methods: Retrospective cohort study of patients (≥18 years) with type 2 diabetes using 2014-2022 electronic health record data from six US care delivery systems. Entry was at earliest pharmacy dispensing of any type 2 diabetes medication. We used multivariable logistic regression to evaluate the association between pharmacy dispensing of SGLT2i and GLP1-RA and race and ethnicity. Findings: Our cohort included 687,165 patients (median 6 years of dispensing data; median 60 years; 0.3% American Indian/Alaska Native (AI/AN), 16.6% Asian, 10.5% Black, 1.4% Hawaiian or Pacific Islander (HPI), 31.1% Hispanic, 3.8% Other, and 36.3% White). SGLT2i was lower for AI/AN (OR 0.80, 95% confidence interval 0.68-0.94), Black (0.89, 0.86-0.92) and Hispanic (0.87, 0.85-0.89) compared to White patients. GLP-1 RA was lower for AI/AN (0.78, 0.63-0.97), Asian (0.50, 0.48-0.53), Black (0.86, 0.83-0.90), HPI (0.52, 0.46-0.57), Hispanic (0.69, 0.66-0.71), and Other (0.78, 0.73-0.83) compared to White patients. Interpretation: Dispensing of SGLT2is, and GLP-1 RAs was lower in minority group patients. There is a need to evaluate approaches to increase use of these cardiorenal protective drugs in patients from racial and ethnic minority groups with type 2 diabetes to reduce adverse cardiorenal outcomes and improve health equity. Funding: Patient-Centered Outcomes Research Institute and National Institutes of Health.
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Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major human pathogens. It could carry numerous resistance genes and virulence factors in its genome, some of which are related to the severity of the infection. An observational, descriptive, cross-sectional study was designed to molecularly analyze MRSA isolates that cause invasive infections in Paraguayan children from 2009 to 2013. Ten representative MRSA isolates of the main clonal complex identified were analyzed with short-read paired-end sequencing and assessed for the virulome, resistome, and phylogenetic relationships. All the genetically linked MRSA isolates were recovered from diverse clinical sources, patients, and hospitals at broad gap periods. The pan-genomic analysis of these clones revealed three major and different clonal complexes (CC30, CC5, and CC8), each composed of clones closely related to each other. The CC30 genomes prove to be a successful clone, strongly installed and disseminated throughout our country, and closely related to other CC30 public genomes from the region and the world. The CC5 shows the highest genetic variability, and the CC8 carried the complete arginine catabolic mobile element (ACME), closely related to the USA300-NAE-ACME+, identified as the major cause of CA-MRSA infections in North America. Multiple virulence and resistance genes were identified for the first time in this study, highlighting the complex virulence profiles of MRSA circulating in the country. This study opens a wide range of new possibilities for future projects and trials to improve the existing knowledge on the epidemiology of MRSA circulating in Paraguay. IMPORTANCE: The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) is a public health problem worldwide. The most frequent MRSA clones identified in Paraguay in previous studies (including community and hospital acquired) were the Pediatric (CC5-ST5-IV), the Cordobes-Chilean (CC5-ST5-I), the SouthWest Pacific (CC30-ST30-IV), and the Brazilian (CC8-ST239-III) clones. In this study, the pan-genomic analysis of the most representative MRSA clones circulating in invasive infection in Paraguayan children over the years 2009-2013, such as the CC30-ST30-IV, CC5-ST5-IV, and CC8-ST8-IV, was carried out to evaluate their genetic diversity, their repertoire of virulence factors, and antimicrobial resistance determinants. This revealed multiple virulence and resistance genes, highlighting the complex virulence profiles of MRSA circulating in Paraguay. Our work is the first genomic study of MRSA in Paraguay and will contribute to the development of genomic surveillance in the region and our understanding of the global epidemiology of this pathogen.
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Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Criança , Infecções Estafilocócicas/tratamento farmacológico , Filogenia , Estudos Transversais , Paraguai/epidemiologia , Genômica , Fatores de Virulência/genética , Células Clonais , Testes de Sensibilidade Microbiana , Antibacterianos/uso terapêuticoRESUMO
PURPOSE: The purpose of this study is to characterize the effect of sex and the influence of oral contraception usage on musculotendinous injury (MTI). Current literature suggests a disparity in the incidence of MTI between males and females. This may be attributed to inherent biological differences between the sexes, such as in the sex hormonal milieu. There is a lack of information associating sex hormone milieu and MTI. METHODS: We searched the PearlDiver database (a for-fee healthcare database) for males, females taking oral contraceptives (OC), and eumenorrheic females not taking any form of hormonal contraceptives (non-OC) 18-39 yr old. The three populations were matched by age and body mass index. We queried the database for lower-extremity skeletal MTI diagnoses in these groups. RESULTS: Each group contained 42,267 patients with orthopedic injuries. There were a total of 1476 (3.49%) skeletal MTI in the male group, 1078 (2.55%) in non-OC females, and 231 (0.55%) in OC females. Both the non-OC and the OC groups had a significantly smaller proportion of MTI than males ( P < 0.0001), and therefore these groups were less likely (adjusted odds ratios, 0.72 and 0.15, respectively) to experience MTI when controlled for potential covariates. CONCLUSIONS: In this study, we show that females are less likely to develop MTI to total injuries, when compared with males, with OC using females being least likely followed by non-OC females. These results are consistent with other epidemiological studies; however, overall results in the literature are variable. This study adds to the emerging body of literature on sex hormone-influenced musculoskeletal injury but, more specifically, MTI, which have not been rigorously investigated.
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Anticoncepção , Anticoncepcionais Orais , Humanos , Masculino , Feminino , Incidência , Hormônios Esteroides GonadaisRESUMO
Prolonged ultraviolet exposure results in the formation of cyclobutane pyrimidine dimers (CPDs) in RNA. Consequently, prebiotic photolesion repair mechanisms should have played an important role in the maintenance of the structural integrity of primitive nucleic acids. 2,6-Diaminopurine is a prebiotic nucleobase that repairs CPDs with high efficiency when incorporated into polymers. We investigate the electronic deactivation pathways of 2,6-diaminopurine-2'-deoxyribose and 9-methyl-2,6-diaminopurine in acetonitrile and aqueous solution to shed light on the photophysical and excited state properties of the 2,6-diaminopurine chromophore. Evidence is presented that both are photostable compounds exhibiting similar deactivation mechanisms upon the population of the S1 (ππ* La ) state at 290 nm. The mechanism involves deactivation through the C2- and C6-reaction coordinates and >99% of the excited state population decays through nonradiative pathways involving two conical intersections with the ground state. The radiative and nonradiative lifetimes are longer in aqueous solution compared to acetonitrile. While τ1 is similar in both derivatives, τ2 is ca. 1.5-fold longer in 2,6-diaminopurine-2'-deoxyribose due to a more efficient trapping in the S1 (ππ* La ) minimum. Therefore, 2,6-diaminopurine could have accumulated in significant quantities during prebiotic times to be incorporated into non-canonical RNA and play a significant role in its photoprotection.
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2-Aminopurina/análogos & derivados , Desoxirribose , Água/química , RNA , Acetonitrilas/químicaRESUMO
BACKGROUND: Population-level tracking of hospital use patterns with integrated care organizations in patients experiencing homelessness has been difficult. A California law implemented in 2019 (Senate Bill 1152) aimed to ensure safety for this population after discharge from the hospital by requiring additional documentation for patients experiencing homelessness, which provides an opportunity to evaluate hospital use by this population. METHODS: In a large integrated health system in California, patients experiencing homelessness were identified through documentation change requirements associated with this law and compared with a matched group from the general population. RESULTS: Patients experiencing homelessness had increased rates of hospital readmission after discharge compared to the general population matched on demographics and medical comorbidity in 2019 and 2020. Any address change in the prior year for patients was associated with increased odds of emergency department readmission. Patients experiencing homelessness, both enrolled in an integrated delivery system and not, were successfully identified as having higher readmission rates compared with their housed counterparts. CONCLUSION: Documentation of housing status following Senate Bill 1152 has enabled improved study of hospital use among those with housing instability. Understanding patterns of hospital use in this vulnerable group will help practitioners identify timely points of intervention for further social and health care support.
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Pessoas Mal Alojadas , Readmissão do Paciente , Humanos , Registros Eletrônicos de Saúde , Habitação , Alta do PacienteRESUMO
In anthropological, medical, and forensic studies, the nonrecombinant region of the human Y chromosome (NRY) enables accurate reconstruction of pedigree relationships and retrieval of ancestral information. Using high-throughput sequencing (HTS) data, we present a benchmarking analysis of command-line tools for NRY haplogroup classification. The evaluation was performed using paired Illumina data from whole-genome sequencing (WGS) and whole-exome sequencing (WES) experiments from 50 unrelated donors. Additionally, as a validation, we also used paired WGS/WES datasets of 54 individuals from the 1000 Genomes Project. Finally, we evaluated the tools on data from third-generation HTS obtained from a subset of donors and one reference sample. Our results show that WES, despite typically offering less genealogical resolution than WGS, is an effective method for determining the NRY haplogroup. Y-LineageTracker and Yleaf showed the highest accuracy for WGS data, classifying precisely 98% and 96% of the samples, respectively. Yleaf outperforms all benchmarked tools in the WES data, classifying approximately 90% of the samples. Yleaf, Y-LineageTracker, and pathPhynder can correctly classify most samples (88%) sequenced with third-generation HTS. As a result, Yleaf provides the best performance for applications that use WGS and WES. Overall, our study offers researchers with a guide that allows them to select the most appropriate tool to analyze the NRY region using both second- and third-generation HTS data.
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Bacterial ribonucleoprotein bodies (BR-bodies) are non-membrane-bound structures that facilitate mRNA decay by concentrating mRNA substrates with RNase E and the associated RNA degradosome machinery. However, the full complement of proteins enriched in BR-bodies has not been defined. Here, we define the protein components of BR-bodies through enrichment of the bodies followed by mass spectrometry-based proteomic analysis. We find 111 BR-body-enriched proteins showing that BR-bodies are more complex than previously assumed. We identify five BR-body-enriched proteins that undergo RNA-dependent phase separation in vitro with a complex network of condensate mixing. We observe that some RNP condensates co-assemble with preferred directionality, suggesting that RNA may be trafficked through RNP condensates in an ordered manner to facilitate mRNA processing/decay, and that some BR-body-associated proteins have the capacity to dissolve the condensate. Altogether, these results suggest that a complex network of protein-protein and protein-RNA interactions controls BR-body phase separation and RNA processing.
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Proteoma , RNA , Proteoma/metabolismo , Proteômica , Ribonucleoproteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
All-organic, heavy-atom-free photosensitizers based on thionation of nucleobases are receiving increased attention because they are easy to make, noncytotoxic, work both in the presence and absence of molecular oxygen, and can be readily incorporated into DNA and RNA. In this contribution, the DNA and RNA fluorescent probe, thieno[3,4-d]pyrimidin-4(1H)-one, has been thionated to develop thieno[3,4-d]pyrimidin-4(3H)-thione, which is nonfluorescent and absorbs near-visible radiation with about 60% higher efficiency. Steady-state absorption and emission spectra are combined with transient absorption spectroscopy and CASPT2 calculations to delineate the electronic relaxation mechanisms of both pyrimidine derivatives in aqueous and acetonitrile solutions. It is demonstrated that thieno[3,4-d]pyrimidin-4(3H)-thione efficiently populates the long-lived and reactive triplet state generating singlet oxygen with a quantum yield of about 80% independent of solvent. It is further shown that thieno[3,4-d]pyrimidin-4(3H)-thione exhibits high photodynamic efficacy against monolayer melanoma cells and cervical cancer cells both under normoxic and hypoxic conditions. Our combined spectroscopic, computational, and in vitro data demonstrate the excellent potential of thieno[3,4-d]pyrimidin-4(1H)-thione as a heavy-atom-free PDT agent and paves the way for further development of photosensitizers based on the thionation of thieno[3,4-d]pyrimidine derivatives. Collectively, the experimental and computational results demonstrate that thieno[3,4-d]pyrimidine-4(3H)-thione stands out as the most promising thiobase photosensitizer developed to this date.
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Transcription factors in phytopathogenic fungi are key players due to their gene expression regulation leading to fungal growth and pathogenicity. The KilA-N family encompasses transcription factors unique to fungi, and the Bqt4 subfamily is included in it and is poorly understood in filamentous fungi. In this study, we evaluated the role in growth and pathogenesis of the homologous of Bqt4, FspTF, in Fusarium sp. isolated from the ambrosia beetle Xylosandrus morigerus through the characterization of a CRISPR/Cas9 edited strain in Fsptf. The phenotypic analysis revealed that TF65-6, the edited strain, modified its mycelia growth and conidia production, exhibited affectation in mycelia and culture pigmentation, and in the response to certain stress conditions. In addition, the plant infection process was compromised. Untargeted metabolomic and transcriptomic analysis, clearly showed that FspTF may regulate secondary metabolism, transmembrane transport, virulence, and diverse metabolic pathways such as lipid metabolism, and signal transduction. These data highlight for the first time the biological relevance of an orthologue of Bqt4 in Fusarium sp. associated with an ambrosia beetle.
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The impacts on the morphological, electrical and hardness properties of thermoplastic polyurethane (TPU) plates using multi-walled carbon nanotubes (MWCNTs) as reinforcing fillers have been investigated, using MWCNT loadings between 1 and 7 wt%. Plates of the TPU/MWCNT nanocomposites were fabricated by compression molding from extruded pellets. An X-ray diffraction analysis showed that the incorporation of MWCNTs into the TPU polymer matrix increases the ordered range of the soft and hard segments. SEM images revealed that the fabrication route used here helped to obtain TPU/MWCNT nanocomposites with a uniform dispersion of the nanotubes inside the TPU matrix and promoted the creation of a conductive network that favors the electronic conduction of the composite. The potential of the impedance spectroscopy technique has been used to determine that the TPU/MWCNT plates exhibited two conduction mechanisms, percolation and tunneling conduction of electrons, and their conductivity values increase as the MWCNT loading increases. Finally, although the fabrication route induced a hardness reduction with respect to the pure TPU, the addition of MWCNT increased the Shore A hardness behavior of the TPU plates.
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Introduction Homelessness contributes to worsening health and increased health care costs. There is little published research that leverages rich electronic health record (EHR) data to predict future homelessness risk and inform interventions to address it. The authors' objective was to develop a model for predicting future homelessness using individual EHR and geographic data covariates. Methods This retrospective cohort study included 2,543,504 adult members (≥ 18 years old) from Kaiser Permanente Northern California and evaluated which covariates predicted a composite outcome of homelessness status (hospital discharge documentation of a homeless patient, medical diagnosis of homelessness, approved medical financial assistance application for homelessness, and/or "homeless/shelter" in address name). The predictors were measured in 2018-2019 and included prior diagnoses and demographic and geographic data. The outcome was measured in 2020. The cohort was split (70:30) into a derivation and validation set, and logistic regression was used to model the outcome. Results Homelessness prevalence was 0.35% in the overall sample. The final logistic regression model included 26 prior diagnoses, demographic, and geographic-level predictors. The regression model using the validation set had moderate sensitivity (80.4%) and specificity (83.2%) for predicting future cases of homelessness and achieved excellent classification properties (area under the curve of 0.891 [95% confidence interval = 0.884-0.897]). Discussion This prediction model can be used as an initial triage step to enhance screening and referral tools for identifying and addressing homelessness, which can improve health and reduce health care costs. Conclusions EHR data can be used to predict chance of homelessness at a population health level.
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Prestação Integrada de Cuidados de Saúde , Pessoas Mal Alojadas , Adulto , Humanos , Adolescente , Estudos Retrospectivos , Habitação , CaliforniaRESUMO
The goal of the study was to characterize muscle activation/deactivation dynamics across the menstrual cycle in healthy young women. Twenty-two healthy eumenorrheic women (age: 27.0 ± 4.4 years; mean ± SD) were tested every other day for one menstrual cycle. Serum estradiol and progesterone were quantified at the time of testing. Peak torque (PT), time to peak torque (TPT), and half relaxation time (HRT) of soleus muscle twitch were measured. Muscle twitch was elicited by delivering 1 ms width electrical pulses to the tibial nerve at an intensity that generated a maximum motor response (S-100) and at supramaximal intensity (S-120; 1.2 × S-100). The analyses were performed for each menstrual cycle phase: 1) the follicular phase to analyze the effect of estradiol while the progesterone concentrations remained at low concentrations; 2) the luteal phase to analyze the effect of progesterone with background estradiol concentrations. In the follicular phase, there was no association of estradiol for PT, TPT, and HRT. In the luteal phase, while estradiol had no association on PT, TPT, and HRT, progesterone expressed a significant association with HRT reduction but no association on PT or TPT. Also, there was a significant estradiol and progesterone interaction for HRT. However, the regression parameters are nearly zero, suggesting that the change in HRT may not have an impact on muscle performance across the menstrual cycle but implications on other women's health conditions with elevated sex hormone concentrations, such as pregnancy, may prove critical.
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On July 23, 2022, monkeypox disease (mpox) was declared a Public Emergency of International Concern (PHEIC) by the World Health Organization (WHO) due to a multicountry outbreak. In Europe, several cases of mpox virus (MPXV) infection related to this outbreak were detected in the Canary Islands (Spain). Here we describe the combination of viral DNA sequencing and bioinformatic approaches, including methods for de novo genome assembly and short- and long-read technologies, used to reconstruct the first MPXV genome isolated in the Canary Islands on the 31st of May 2022 from a male adult patient with mild symptoms. The same sequencing and bioinformatic approaches were then validated with three other positive cases of MPXV infection from the same mpox outbreak. We obtained the best results using a reference-based approach with short reads, evidencing 46-79 nucleotide variants against viral sequences from the 2018-2019 mpox outbreak and placing the viral sequences in the new B.1 sublineage of clade IIb of the MPXV classification. This study of MPXV demonstrates the potential of metagenomics sequencing for rapid and precise pathogen identification.
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The coronavirus disease 2019 (COVID-19) pandemic has resulted in significant lifestyle changes due to shelter-in-place confinement orders. The study's purpose was to assess if the COVID-19 pandemic affected self-reported diabetes prevention behaviors among American adults with prediabetes. As part of a randomized clinical trial among adults with prediabetes and overweight/obesity, questions were added to existing study surveys to assess the effect of the COVID-19 pandemic on diabetes prevention behaviors and stress. Survey responses were summarized using frequencies. 259 study participants completed seven COVID-19 survey questions from June 2020 to June 2021. Participants were 62.9% female, 42.5% White, 31.3% Black, 11.6% Asian, 8.1% Hispanic, and 6.6% Other. Over 75% of participants reported that the COVID-19 pandemic affected physical activity levels, with 82.1% of those affected reporting decreased physical activity; 70.3% reported that the pandemic affected their eating habits, with 61.7% of those affected reporting their eating habits became less healthy; 73.7% reported that the pandemic affected their level of stress, with 97.4% of those affected reporting that their level of stress had increased; 60% reported that the pandemic affected their motivation to adopt/maintain healthy habits, with 72.9% of those affected reporting their motivation decreased. A high percentage of study participants with prediabetes reported decreases in health promotion behaviors and increases in stress due to the COVID-19 pandemic. Consequently, the pandemic could lead to increased diabetes incidence. Strategies to improve diabetes prevention behaviors and address mental health concerns among those at-risk for diabetes are critical during and after the COVID-19 pandemic.