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Genetic and fragmented palaeoanthropological data suggest that Denisovans were once widely distributed across eastern Eurasia1-3. Despite limited archaeological evidence, this indicates that Denisovans were capable of adapting to a highly diverse range of environments. Here we integrate zooarchaeological and proteomic analyses of the late Middle to Late Pleistocene faunal assemblage from Baishiya Karst Cave on the Tibetan Plateau, where a Denisovan mandible and Denisovan sedimentary mitochondrial DNA were found3,4. Using zooarchaeology by mass spectrometry, we identify a new hominin rib specimen that dates to approximately 48-32 thousand years ago (layer 3). Shotgun proteomic analysis taxonomically assigns this specimen to the Denisovan lineage, extending their presence at Baishiya Karst Cave well into the Late Pleistocene. Throughout the stratigraphic sequence, the faunal assemblage is dominated by Caprinae, together with megaherbivores, carnivores, small mammals and birds. The high proportion of anthropogenic modifications on the bone surfaces suggests that Denisovans were the primary agent of faunal accumulation. The chaîne opératoire of carcass processing indicates that animal taxa were exploited for their meat, marrow and hides, while bone was also used as raw material for the production of tools. Our results shed light on the behaviour of Denisovans and their adaptations to the diverse and fluctuating environments of the late Middle and Late Pleistocene of eastern Eurasia.
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Arqueología , Huesos , Cuevas , Fósiles , Hominidae , Animales , Asia , Aves , Huesos/química , Carnívoros , Europa (Continente) , Herbivoria , Historia Antigua , Hominidae/clasificación , Espectrometría de Masas , Carne/historia , Filogenia , Proteómica , Costillas/química , Comportamiento del Uso de la HerramientaRESUMEN
During development, neurons achieve a stereotyped neuron type-specific morphology, which relies on dynamic support by microtubules (MTs). An important player is the augmin complex (hereafter augmin), which binds to existing MT filaments and recruits the γ-tubulin ring complex (γ-TuRC), to form branched MTs. In cultured neurons, augmin is important for neurite formation. However, little is known about the role of augmin during neurite formation in vivo. Here, we have revisited the role of mammalian augmin in culture and then turned towards the class four Drosophila dendritic arborization (c4da) neurons. We show that MT density is maintained through augmin in cooperation with the γ-TuRC in vivo. Mutant c4da neurons show a reduction of newly emerging higher-order dendritic branches and in turn also a reduced number of their characteristic space-filling higher-order branchlets. Taken together, our data reveal a cooperative function for augmin with the γ-TuRC in forming enough MTs needed for the appropriate differentiation of morphologically complex dendrites in vivo.
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Dendritas , Proteínas de Drosophila , Proteínas Asociadas a Microtúbulos , Microtúbulos , Animales , Microtúbulos/metabolismo , Dendritas/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Asociadas a Microtúbulos/genética , Drosophila melanogaster/metabolismo , Tubulina (Proteína)/metabolismo , Drosophila/metabolismo , Humanos , Neuronas/metabolismo , Neuronas/citologíaRESUMEN
Global climate change is increasing both average temperatures and the frequencies of extreme high temperatures. Past studies have documented a strong negative effect of exposures to temperatures >30°C on hybrid maize yields. However, these studies could not disentangle genetic adaptation via artificial selection from changes in agronomic practices. Because most of the earliest maize hybrids are no longer available, side-by-side comparisons with modern hybrids under current field conditions are generally impossible. Here, we report on the collection and curation of 81 years of public yield trial records covering 4,730 maize hybrids, which enabled us to model genetic variation for temperature responses among maize hybrids. We show that selection may have indirectly and inconsistently contributed to the genetic adaptation of maize to moderate heat stress over this time period while preserving genetic variance for continued adaptation. However, our results reveal the existence of a genetic tradeoff for tolerance to moderate and severe heat stress, leading to a decrease in tolerance to severe heat stress over the same time period. Both trends are particularly conspicuous since the mid-1970s. Such a tradeoff poses challenges to the continued adaptation of maize to warming climates due to a projected increase in the frequency of extreme heat events. Nevertheless, given recent advances in phenomics, enviromics, and physiological modeling, our results offer a degree of optimism for the capacity of plant breeders to adapt maize to warming climates, assuming appropriate levels of R&D investment.
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Agricultura , Zea mays , Zea mays/genética , Agricultura/métodos , Temperatura , Cambio Climático , Respuesta al Choque Térmico/genéticaRESUMEN
MOTIVATION: It is difficult to generate new molecules with desirable bioactivity through ligand-based de novo drug design, and receptor-based de novo drug design is constrained by disease target information availability. The combination of artificial intelligence and phenotype-based de novo drug design can generate new bioactive molecules, independent from disease target information. Gene expression profiles can be used to characterize biological phenotypes. The Transformer model can be utilized to capture the associations between gene expression profiles and molecular structures due to its remarkable ability in processing contextual information. RESULTS: We propose TransGEM (Transformer-based model from gene expression to molecules), which is a phenotype-based de novo drug design model. A specialized gene expression encoder is used to embed gene expression difference values between diseased cell lines and their corresponding normal tissue cells into TransGEM model. The results demonstrate that the TransGEM model can generate molecules with desirable evaluation metrics and property distributions. Case studies illustrate that TransGEM model can generate structurally novel molecules with good binding affinity to disease target proteins. The majority of genes with high attention scores obtained from TransGEM model are associated with the onset of the disease, indicating the potential of these genes as disease targets. Therefore, this study provides a new paradigm for de novo drug design, and it will promote phenotype-based drug discovery. AVAILABILITY AND IMPLEMENTATION: The code is available at https://github.com/hzauzqy/TransGEM.
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Diseño de Fármacos , Humanos , Fenotipo , Perfilación de la Expresión Génica/métodos , Inteligencia Artificial , Algoritmos , Expresión Génica , LigandosRESUMEN
G-quadruplex (G4) is a unique secondary structure formed by guanine-rich nucleic acid sequences. Growing studies reported that the genomes of some viruses harbor G4 structures associated with viral replication, opening up a new field to dissect viral infection. Porcine reproductive and respiratory syndrome virus (PRRSV), a representative member of Arteriviridae, is an economically significant pathogen that has devastated the swine industry worldwide for over 30 years. In this study, we identified a highly conserved G-rich sequence with parallel-type G4 structure (named PRRSV-G4) in the negative strand genome RNA of PRRSV. Pyridostatin (PDS), a well-known G4-binding ligand, stabilized the PRRSV-G4 structure and inhibited viral replication. By screening the proteins interacting with PRRSV-G4 in PRRSV-infected cells and single-molecule magnetic tweezers analysis, we found that two helicases, host DDX18 and viral nsp10, interact with and efficiently unwound the PRRSV-G4 structure, thereby facilitating viral replication. Using a PRRSV reverse genetics system, we confirmed that recombinant PRRSV with a G4-disruptive mutation exhibited resistance to PDS treatment, thereby displaying higher replication than wild-type PRRSV. Collectively, these results demonstrate that the PRRSV-G4 structure plays a crucial regulatory role in viral replication, and targeting this structure represents a promising strategy for antiviral therapies.
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Virus del Síndrome Respiratorio y Reproductivo Porcino , Porcinos , Animales , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , Virus del Síndrome Respiratorio y Reproductivo Porcino/metabolismo , Proteínas no Estructurales Virales/metabolismo , ADN Helicasas/genética , Replicación Viral/genética , ARNRESUMEN
Planar hexagonal boron nitride (h-BN) and tubular BN nanotube (BNNT), known for their superior mechanical and thermal properties, as well as wide electronic band gap, hold great potential for nanoelectronic and optoelectronic devices. Chemical vapor deposition has demonstrated the best way to scalable synthesis of high-quality BN nanomaterials. Yet, the atomistic understanding of reactions from precursors to product-material remains elusive, posing challenges for experimental design. Here, performing first-principles calculations and ab initio molecular simulations, we explore pyrolytic decomposition pathways of the most used precursor ammonia borane (H3BNH3, AB) to BN, in gas-phase and on Ni(111) or amorphous boron (for BNNT growth) surfaces, for comparison. It reveals that in the gas phase, a pair of AB molecules cooperate to form intermediate NH3 and ammonia diborane, which further dissociates into H2BNH2, accompanied by critical BH4- and NH4+ ions. These ions act as H scavengers facilitating H2BNH2 dehydrogenation into HBNH. The consequent HBNH directly feeds BN flake growth by reacting with the crystal edge, while the addition of H2BNH2 to the edge is prohibited at 1500 K. In contrast, on Ni and boron surfaces, AB monomer dehydrogenates stepwise, deeper, yielding BNH and BN dimer as the primary building unit. Our study maps out three typical experimental conditions regarding the dissociation of AB-precursor, providing insights into the underlying reaction mechanisms of gas-phase precursors, to help as guidelines for the experimental growth of BN nanomaterials.
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We constructed a photoanode comprising the homogeneous water oxidation catalyst (WOC) Na8K8[Co9(H2O)6(OH)3(HPO4)2(PW9O34)3] (Co9POM) and nanoporous n-type TiO2 photoelectrodes (henceforth "TiO2-Co9POM") by first anchoring the cationic 3-aminopropyltrimethoxysilane (APS) ligand on a metal oxide light absorber, followed by treatment of the metal oxide-APS with a solution of the polyoxometalate WOC. The resulting TiO2-Co9POM photoelectrode exhibits a 3-fold oxygen evolution photocurrent enhancement compared to bare TiO2 in aqueous acidic conditions. Three-element (Co 2p, W 4f, and O 1s) X-ray photoelectron spectroscopy and Raman spectroscopy studies before and after use indicate that surface-bound Co9POM retains its structural integrity throughout all photoelectrochemical water oxidation studies reported here. Extensive charge-transfer mechanistic studies by photoelectrochemical techniques and transient absorption spectroscopy elucidate that Co9POM serves as an efficient WOC, extracting photogenerated holes from TiO2 on the picosecond time scale. This is the first comprehensive mechanistic investigation elucidating the roles of polyoxometalates in POM-photoelectrode hybrid oxygen evolution reaction systems.
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OBJECTIVE: Both low serum albumin (SA) concentration and coronary microvascular dysfunction (CMD) are risk factors for the development of heart failure (HF). We hypothesized that SA concentration is associated with myocardial flow reserve (MFR) and implicated in pathophysiological mechanism of HF. METHODS: We retrospectively studied 454 patients undergoing dynamic cardiac cadmium-zinc-telluride myocardial perfusion imaging from April 2018 to February 2020. The population was categorized into three groups according to SA level (g/dL): Group 1: >4, Group 2: 3.5-4, and Group 3: <3.5. Myocardial blood flow (MBF) and myocardial flow reserve (MFR, defined as stress/rest MBF ratio) were compared. RESULTS: The mean age of the whole cohort was 66.2 years, and 65.2% were men. As SA decreased, stress MBF (mL min-1 g-1) and MFR decreased (MBF: 3.29 ± 1.03, MFR: 3.46 ± 1.33 in Group 1, MBF: 2.95 ± 1.13, MFR: 2.51 ± 0.93 in Group 2, and MBF: 2.64 ± 1.16, MFR: 1.90 ± 0.50 in Group 3), whereas rest MBF (mL min-1 g-1) increased (MBF: 1.05 ± 0.42 in Group 1, 1.27 ± 0.56 in Group 2, and 1.41 ± 0.61 in Group 3). After adjusting for covariates, compared with Group 1, the odds ratios for impaired MFR (defined as MFR < 2.5) were 3.57 (95% CI: 2.32-5.48) for Group 2 and 34.9 (95% CI: 13.23-92.14) for Group 3. The results would be similar if only regional MFR were assessed. The risk prediction for CMD using SA was acceptable, with an AUC of 0.76. CONCLUSION: Low SA concentration was associated with the severity of CMD in both global and regional MFR as well as MBF.
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Cadmio , Circulación Coronaria , Telurio , Tomografía Computarizada de Emisión de Fotón Único , Zinc , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Zinc/sangre , Cadmio/sangre , Microcirculación , Imagen de Perfusión Miocárdica/métodos , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico por imagen , Compuestos de Zinc , Albúmina SéricaRESUMEN
IMPORTANCE: Retrograde transport has been reported to be closely associated with normal cellular biological processes and viral replication. As an emerging enteropathogenic coronavirus with zoonotic potential, porcine deltacoronavirus (PDCoV) has attracted considerable attention. However, whether retrograde transport is associated with PDCoV infection remains unclear. Our present study demonstrates that retromer protein VPS35 acts as a critical host factor that is required for PDCoV infection. Mechanically, VPS35 interacts with PDCoV NS6, mediating the retrograde transport of NS6 from endosomes to the Golgi and preventing it from lysosomal degradation. Recombinant PDCoVs with an NS6 deletion display resistance to VPS35 deficiency. Our work reveals a novel evasion mechanism of PDCoV that involves the manipulation of the retrograde transport pathway by VPS35, providing new insight into the mechanism of PDCoV infection.
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Infecciones por Coronavirus , Coronavirus , Enfermedades de los Porcinos , Proteínas de Transporte Vesicular , Proteínas Reguladoras y Accesorias Virales , Animales , Coronavirus/genética , Coronavirus/metabolismo , Deltacoronavirus , Porcinos , Replicación Viral , Proteínas Reguladoras y Accesorias Virales/genética , Proteínas Reguladoras y Accesorias Virales/metabolismo , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismoRESUMEN
Phenotypic plasticity describes a genotype's ability to produce different phenotypes in response to different environments. Breeding crops that exhibit appropriate levels of plasticity for future climates will be crucial to meeting global demand, but knowledge of the critical environmental factors is limited to a handful of well-studied major crops. Using 727 maize (Zea mays L.) hybrids phenotyped for grain yield in 45 environments, we investigated the ability of a genetic algorithm and two other methods to identify environmental determinants of grain yield from a large set of candidate environmental variables constructed using minimal assumptions. The genetic algorithm identified pre- and postanthesis maximum temperature, mid-season solar radiation, and whole season net evapotranspiration as the four most important variables from a candidate set of 9150. Importantly, these four variables are supported by previous literature. After calculating reaction norms for each environmental variable, candidate genes were identified and gene annotations investigated to demonstrate how this method can generate insights into phenotypic plasticity. The genetic algorithm successfully identified known environmental determinants of hybrid maize grain yield. This demonstrates that the methodology could be applied to other less well-studied phenotypes and crops to improve understanding of phenotypic plasticity and facilitate breeding crops for future climates.
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Plants delicately regulate endogenous auxin levels through the coordination of transport, biosynthesis, and inactivation, which is crucial for growth and development. While it is well-established that the actin cytoskeleton can regulate auxin levels by affecting polar transport, its potential role in auxin biosynthesis has remained largely unexplored. Using LC-MS/MS-based methods combined with fluorescent auxin marker detection, we observed a significant increase in root auxin levels upon deletion of the actin bundling proteins AtFIM4 and AtFIM5. Fluorescent observation, immunoblotting analysis, and biochemical approaches revealed that AtFIM4 and AtFIM5 affect the protein abundance of the key auxin synthesis enzyme YUC8 in roots. AtFIM4 and AtFIM5 regulate the auxin synthesis enzyme YUC8 at the protein level, with its degradation mediated by the 26S proteasome. This regulation modulates auxin synthesis and endogenous auxin levels in roots, consequently impacting root development. Based on these findings, we propose a molecular pathway centered on the 'actin cytoskeleton-26S proteasome-YUC8-auxin' axis that controls auxin levels. Our findings shed light on a new pathway through which plants regulate auxin synthesis. Moreover, this study illuminates a newfound role of the actin cytoskeleton in regulating plant growth and development, particularly through its involvement in maintaining protein homeostasis via the 26S proteasome.
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Highly collimated and directional backlights are essential for realizing advanced display technologies such as autostereoscopic 3D displays. Previously reported collimated backlights, either edge-lit or direct-lit, in general still suffer unsatisfactory form factors, directivity, uniformity, or crosstalk etc. In this work, we report a simple stacking architecture for the highly collimated and uniform backlights, by combining linear light source arrays and carefully designed cylindrical lens arrays. Experiments were conducted to validate the design and simulation, using the conventional edge-lit backlight or the direct-lit mini-LED (mLED) arrays as light sources, the NiFe (stainless steel) barrier sheets, and cylindrical lens arrays fabricated by molding. Highly collimated backlights with small angular divergence of ±1.45°â¼±2.61°, decent uniformity of 93-96%, and minimal larger-angle sidelobes in emission patterns were achieved with controlled divergence of the light source and optimization of lens designs. The architecture reported here provides a convenient way to convert available backlight sources into a highly collimated backlight, and the use of optically reflective barrier also helps recycle light energy and enhance the luminance. The results of this work are believed to provide a facile approach for display technologies requiring highly collimated backlights.
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BACKGROUND: To describe the methodology for conducting the CalScope study, a remote, population-based survey launched by the California Department of Public Health (CDPH) to estimate SARS-CoV-2 seroprevalence and understand COVID-19 disease burden in California. METHODS: Between April 2021 and August 2022, 666,857 randomly selected households were invited by mail to complete an online survey and at-home test kit for up to one adult and one child. A gift card was given for each completed survey and test kit. Multiple customized REDCap databases were used to create a data system which provided task automation and scalable data management through API integrations. Support infrastructure was developed to manage follow-up for participant questions and a communications plan was used for outreach through local partners. RESULTS: Across 3 waves, 32,671 out of 666,857 (4.9%) households registered, 6.3% by phone using an interactive voice response (IVR) system and 95.7% in English. Overall, 25,488 (78.0%) households completed surveys, while 23,396 (71.6%) households returned blood samples for testing. Support requests (n = 5,807) received through the web-based form (36.3%), by email (34.1%), and voicemail (29.7%) were mostly concerned with the test kit (31.6%), test result (26.8%), and gift card (21.3%). CONCLUSIONS: Ensuring a well-integrated and scalable data system, responsive support infrastructure for participant follow-up, and appropriate academic and local health department partnerships for study management and communication allowed for successful rollout of a large population-based survey. Remote data collection utilizing online surveys and at-home test kits can complement routine surveillance data for a state health department.
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COVID-19 , Pruebas con Sangre Seca , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/diagnóstico , Estudios Seroepidemiológicos , California/epidemiología , SARS-CoV-2/inmunología , Pruebas con Sangre Seca/métodos , Pruebas con Sangre Seca/estadística & datos numéricos , Adulto , Encuestas y Cuestionarios , Masculino , Femenino , Niño , Persona de Mediana Edad , AdolescenteRESUMEN
Rationale: Indoor air pollution represents a modifiable risk factor for respiratory morbidity in chronic obstructive pulmonary disease (COPD). The effects of indoor air pollution, as well as the impact of interventions to improve indoor air quality, on cardiovascular morbidity in COPD remain unknown. Objectives: To determine the association between indoor particulate matter (PM) and heart rate variability (HRV), a measure of cardiac autonomic function tied to cardiovascular morbidity and mortality, as well as the impact of household air purifiers on HRV. Methods: Former smokers with moderate-severe COPD were recruited from a 6-month randomized controlled trial of a portable air cleaner intervention to undergo paired assessment of both in-home PM and HRV using 24-hour Holter monitoring at up to five time points. Primary outcomes were HRV measures tied to cardiovascular morbidity (standard deviation of normal-to-normal intervals [SDNN] and root mean square of successive differences between normal-to-normal intervals [RMSSD]). Measurements and Results: Eighty-five participants contributed 317 HRV measurements. A twofold increase in household PM ⩽2.5 µm in aerodynamic diameter was associated with decreases in SDNN (ß, -2.98% [95% confidence interval (CI), -5.12 to -0.78]) and RMSSD (ß, -4.57% [95% CI, -10.1 to -1.60]). The greatest effects were observed with ultrafine particles (<100 nm) (RMSSD; ß, -16.4% [95% CI, -22.3 to -10.1]) and among obese participants. Participants randomized to the active air cleaner saw improvements in RMSSD (ß, 25.2% [95% CI, 2.99 to 52.1]), but not SDNN (ß, 2.65% [95% CI, -10.8 to 18.1]), compared with the placebo group. Conclusions: This is the first U.S. study to describe the association between household PM and cardiac autonomic function among individuals with COPD, as well as the potential cardiovascular health benefits of household air cleaners.
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Contaminantes Atmosféricos , Contaminación del Aire Interior , Contaminación del Aire , Enfermedades Cardiovasculares , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Contaminación del Aire Interior/efectos adversos , Material Particulado/efectos adversos , Corazón , Frecuencia Cardíaca/fisiología , Contaminantes Atmosféricos/efectos adversosRESUMEN
Rationale: Strict adherence to procedural protocols and diagnostic definitions is critical to understand the efficacy of new technologies. Electromagnetic navigational bronchoscopy (ENB) for lung nodule biopsy has been used for decades without a solid understanding of its efficacy, but offers the opportunity for simultaneous tissue acquisition via electromagnetic navigational transthoracic biopsy (EMN-TTNA) and staging via endobronchial ultrasound (EBUS). Objective: To evaluate the diagnostic yield of EBUS, ENB, and EMN-TTNA during a single procedure using a strict a priori definition of diagnostic yield with central pathology adjudication. Methods: A prospective, single-arm trial was conducted at eight centers enrolling participants with pulmonary nodules (<3 cm; without computed tomography [CT]- and/or positron emission tomography-positive mediastinal lymph nodes) who underwent a staged procedure with same-day CT, EBUS, ENB, and EMN-TTNA. The procedure was staged such that, when a diagnosis had been achieved via rapid on-site pathologic evaluation, the procedure was ended and subsequent biopsy modalities were not attempted. A study finding was diagnostic if an independent pathology core laboratory confirmed malignancy or a definitive benign finding. The primary endpoint was the diagnostic yield of the combination of CT, EBUS, ENB, and EMN-TTNA. Measurements and Main Results: A total of 160 participants at 8 centers with a mean nodule size of 18 ± 6 mm were enrolled. The diagnostic yield of the combined procedure was 59% (94 of 160; 95% confidence interval [CI], 51-66%). Nodule regression was found on same-day CT in 2.5% of cases (4 of 160; 95% CI, 0.69-6.3%), and EBUS confirmed malignancy in 7.1% of cases (11 of 156; 95% CI, 3.6-12%). The yield of ENB alone was 49% (74 of 150; 95% CI, 41-58%), that of EMN-TTNA alone was 27% (8 of 30; 95% CI, 12-46%), and that of ENB plus EMN-TTNA was 53% (79 of 150; 95% CI, 44-61%). Complications included a pneumothorax rate of 10% and a 2% bleeding rate. When EMN-TTNA was performed, the pneumothorax rate was 30%. Conclusions: The diagnostic yield for ENB is 49%, which increases to 59% with the addition of same-day CT, EBUS, and EMN-TTNA, lower than in prior reports in the literature. The high complication rate and low diagnostic yield of EMN-TTNA does not support its routine use. Clinical trial registered with www.clinicaltrials.gov (NCT03338049).
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Spinal surgeries are accompanied by excessive pain due to extensive dissection and muscle retraction during the procedure. Thoracolumbar interfascial plane (TLIP) blocks for spinal surgeries are a recent addition to regional anesthesia to improve postoperative pain management. When performing a classical TLIP (cTLIP) block, anesthetics are injected between the muscle (m.) multifidus and m. longissimus. During a modified TLIP (mTLIP) block, anesthetics are injected between the m. longissimus and m. iliocostalis instead. Our systematic review provides a comprehensive evaluation of the effectiveness of TLIP blocks in improving postoperative outcomes in spinal surgery through an analysis of randomized controlled trials (RCTs).We conducted a systematic review based on the PRISMA guidelines using PubMed and Scopus databases. Inclusion criteria required studies to be RCTs in English that used TLIP blocks during spinal surgery and report both outcome measures. Outcome data includes postoperative opioid consumption and pain.A total of 17 RCTs were included. The use of a TLIP block significantly decreases postoperative opioid use and pain compared to using general anesthesia (GA) plus 0.9% saline with no increase in complications. There were mixed outcomes when compared against wound infiltration with local anesthesia. When compared with erector spinae plane blocks (ESPB), TLIP blocks often decreased analgesic use, however, this did not always translate to decreased pain. The cTLIP and mTLP block methods had comparable postoperative outcomes but the mTLIP block had a significantly higher percentage of one-time block success.The accumulation of the current literature demonstrates that TLIP blocks are superior to non-block procedures in terms of analgesia requirements and reported pain throughout the hospitalization in patients who underwent spinal surgery. The various levels of success seen with wound infiltration and ESPB could be due to the nature of the different spinal procedures. For example, studies that saw superiority with TLIP blocks included fusion surgeries which is a more invasive procedure resulting in increased postoperative pain compared to discectomies.The results of our systematic review include moderate-quality evidence that show TLIP blocks provide effective pain control after spinal surgery. Although, the application of mTLIP blocks is more successful, more studies are needed to confirm that superiority of mTLIP over cTLIP blocks. Additionally, further high-quality research is needed to verify the potential benefit of TLIP blocks as a common practice for spinal surgeries.
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Bloqueo Nervioso , Dolor Postoperatorio , Humanos , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/tratamiento farmacológico , Bloqueo Nervioso/métodos , Anestésicos Locales/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Músculos Paraespinales , Columna Vertebral/cirugía , Manejo del Dolor/métodosRESUMEN
The outbreak of COVID-19 caused by SARS-CoV-2 has resulted in more than 50 million confirmed cases and over 1 million deaths worldwide as of November 2020. Currently, there are no effective antivirals approved by the Food and Drug Administration to contain this pandemic except the antiviral agent remdesivir. In addition, the trimeric spike protein on the viral surface is highly glycosylated and almost 200,000 variants with mutations at more than 1,000 positions in its 1,273 amino acid sequence were reported, posing a major challenge in the development of antibodies and vaccines. It is therefore urgently needed to have alternative and timely treatments for the disease. In this study, we used a cell-based infection assay to screen more than 3,000 agents used in humans and animals, including 2,855 small molecules and 190 traditional herbal medicines, and identified 15 active small molecules in concentrations ranging from 0.1 nM to 50 µM. Two enzymatic assays, along with molecular modeling, were then developed to confirm those targeting the virus 3CL protease and the RNA-dependent RNA polymerase. Several water extracts of herbal medicines were active in the cell-based assay and could be further developed as plant-derived anti-SARS-CoV-2 agents. Some of the active compounds identified in the screen were further tested in vivo, and it was found that mefloquine, nelfinavir, and extracts of Ganoderma lucidum (RF3), Perilla frutescens, and Mentha haplocalyx were effective in a challenge study using hamsters as disease model.
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Antivirales/farmacología , Tratamiento Farmacológico de COVID-19 , SARS-CoV-2/efectos de los fármacos , Adulto , Animales , Antivirales/química , Antivirales/uso terapéutico , COVID-19/epidemiología , COVID-19/virología , Chlorocebus aethiops , Cricetinae , Modelos Animales de Enfermedad , Reposicionamiento de Medicamentos/métodos , Femenino , Humanos , Masculino , Pandemias , Extractos Vegetales/farmacología , SARS-CoV-2/genética , Células VeroRESUMEN
Optimal early-life care of surplus calves born on dairy farms is critical for health and welfare. This cross-sectional study aimed to describe the marketing practices of male dairy calves, differences in the colostrum management between male and female calves on dairy farms, and the relationship between discrepant colostrum practices and dairy producers' attitudes toward male calf care. United States dairy producers (n = 1,000) in the states of Florida, Michigan, Ohio, Vermont, and Wisconsin were selected using stratified random sampling. A questionnaire containing questions about farm demographics, colostrum management (including quantity and timeliness of colostrum delivery), and producers' attitudes toward male calf care was mailed in February 2021. Attitudes toward male calf care were assessed using 5-point Likert scales for 10 statements regarding perceptions of the value of male calves and barriers in providing optimal care. Producer responses to questions about the quantity and timeliness of colostrum delivery between male and female calves were compared using a nonparametric Wilcoxon rank-sum test. Multivariable logistic regression models were used to investigate the association between differences in colostrum management and producers' attitudes. By May 2021, 953 surveys were delivered and 315 (33.1%) were returned with complete responses. Most producers (>90%) reported feeding equal volumes of colostrum and performing the first postbirth feeding within a similar time frame for male and female calves. However, compared with females, male calves had a longer delay to the first colostrum feeding. Approximately 40% of producers marketed their male calves through auctions, and over half (54.6%) of farms sold the male calves between 3 and 10 d of age. Large farms (≥500 lactating cows) were found to market male calves at a younger age (≤3 d of age). Most producers (>78%) believed their male calves were receiving optimal care and did not consider the workload and financial costs as obstacles to providing good care to male calves. However, those who viewed the workload as an obstacle to good care and produced organic products were marginally more likely to feed a lower volume of colostrum to male calves in the first feeding after birth. These findings suggest that interventions to improve colostrum practices should be more broadly targeted to all calves born on dairy farms, and that age at transport is markedly different between large and small farms.
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Calostro , Industria Lechera , Animales , Bovinos , Masculino , Femenino , Estudios Transversales , Encuestas y Cuestionarios , Mercadotecnía , ActitudRESUMEN
Transportation significantly affects the health and welfare of surplus dairy calves, largely due to the various stressors and pathogen exposures encountered during the process. Concurrently, an animal's microbiome is known to correlate with its health status, with stress-induced alterations in the microbiota potentially precipitating various diseases. This study aimed to compare the effects of transportation durations of 6, 12, or 16 h on the fecal microbiota in young surplus dairy calves. We used a randomized controlled design in which surplus dairy calves aged 1 to 19 d from 5 commercial dairy farms in Ontario were allocated into 1 of 3 transportation groups (6, 12, and 16 h of continuous transportation). Health assessments were conducted before, immediately after, and for 2 wk following transportation. Fecal samples were collected before, immediately after, and at 24 and 72 h after transportation and subjected to 16S rRNA sequencing. Alpha diversity metrics showed no significant differences between the 3 transportation groups at any of the sampling time points. Although ß diversity metrics revealed no clustering by transportation groups, they indicated significant differences across sampling time points within each group. The overall analysis revealed a total of 22 phyla and 353 genera, with Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Fusobacteria being the most abundant phyla. Bacteroides, Escherichia/Shigella, Lactobacillus, Collinsella, and Bifidobacterium were the most abundant genera. The reduction in Fusobacteria abundance before and after transport was significantly larger in the 16-h transportation group when compared with the 6-h transportation group. We also identified several genus-level and amplicon sequence variation-level taxa that displayed significant differences in their abundances across various transportation groups, observed at all sampling time points investigated. This research identifies microbiota changes due to varying transportation durations in surplus dairy calves, providing a broad understanding of the microbial shifts in surplus dairy calves after transportation across varying durations. Although these variations may not directly correlate with overall calf health or indicate dysbiosis, these results emphasize the importance of further investigating transportation practices to enhance calf health and well-being. Further studies are warranted to elucidate the relationship between microbiota and calf health.
Asunto(s)
Heces , Transportes , Animales , Bovinos , Heces/microbiología , Microbiota , ARN Ribosómico 16S , OntarioRESUMEN
BACKGROUND: The risk assessment for survival in heart failure (HF) remains one of the key focuses of research. This study aims to develop a simple and feasible nomogram model for survival in HF based on the Heart Failure-A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) to support clinical decision-making. METHODS: The HF patients were extracted from the HF-ACTION database and randomly divided into a training cohort and a validation cohort at a ratio of 7:3. Multivariate Cox regression was used to identify and integrate significant prognostic factors to form a nomogram, which was displayed in the form of a static nomogram. Bootstrap resampling (resampling = 1000) and cross-validation was used to internally validate the model. The prognostic performance of the model was measured by the concordance index (C-index), calibration curve, and the decision curve analysis. RESULTS: There were 1394 patients with HF in the overall analysis. Seven prognostic factors, which included age, body mass index (BMI), sex, diastolic blood pressure (DBP), exercise duration, peak exercise oxygen consumption (peak VO2), and loop diuretic, were identified and applied to the nomogram construction based on the training cohort. The C-index of this model in the training cohort was 0.715 (95% confidence interval (CI): 0.700, 0.766) and 0.662 (95% CI: 0.646, 0.752) in the validation cohort. The area under the ROC curve (AUC) value of 365- and 730-day survival is (0.731, 0.734) and (0.640, 0.693) respectively in the training cohort and validation cohort. The calibration curve showed good consistency between nomogram-predicted survival and actual observed survival. The decision curve analysis (DCA) revealed net benefit is higher than the reference line in a narrow range of cutoff probabilities and the result of cross-validation indicates that the model performance is relatively robust. CONCLUSIONS: This study created a nomogram prognostic model for survival in HF based on a large American population, which can provide additional decision information for the risk prediction of HF.