ABSTRACT
The NuA3 complex is a major regulator of gene transcription and the cell cycle in yeast. Five core subunits are required for complex assembly and function, but it remains unclear how these subunits interact to form the complex. Here, we report that the Taf14 subunit of the NuA3 complex binds to two other subunits of the complex, Yng1 and Sas3, and describe the molecular mechanism by which the extra-terminal domain of Taf14 recognizes the conserved motif present in Yng1 and Sas3. Structural, biochemical, and mutational analyses show that two motifs are sandwiched between the two extra-terminal domains of Taf14. The head-to-toe dimeric complex enhances the DNA binding activity of Taf14, and the formation of the hetero-dimer involving the motifs of Yng1 and Sas3 is driven by sequence complementarity. In vivo assays in yeast demonstrate that the interactions of Taf14 with both Sas3 and Yng1 are required for proper function of the NuA3 complex in gene transcription and DNA repair. Our findings suggest a potential basis for the assembly of three core subunits of the NuA3 complex, Taf14, Yng1 and Sas3.
Subject(s)
Protein Binding , Saccharomyces cerevisiae Proteins , Saccharomyces cerevisiae , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/chemistry , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Transcription Factor TFIID/metabolism , Transcription Factor TFIID/genetics , Transcription Factor TFIID/chemistry , Protein Subunits/metabolism , Protein Subunits/genetics , TATA-Binding Protein Associated Factors/metabolism , TATA-Binding Protein Associated Factors/genetics , TATA-Binding Protein Associated Factors/chemistry , Histone Acetyltransferases/metabolism , Histone Acetyltransferases/genetics , Protein Multimerization , Models, Molecular , Transcription, Genetic , Amino Acid SequenceABSTRACT
Little is known about the incidence and outcome of high-risk pregnancies in equine practice and clinical studies on spontaneous occurring placentitis cases and treatments are missing. Therefore, the aims of this retrospective field study were to (1) describe the incidence and severity of ultrasonographic assessed placental abnormalities (UPA) in 4,192 pregnancies on a large commercial warmblood stud farm in 2017 - 2019 and (2) characterize these UPA cases and their pregnancy outcome. UPA severity (Placental abnormality score (PSc) 1-3; low to high), nine treatment regimens (TM1-9) used in UPA cases and treatment duration as well as subsequent fertility were analyzed in the group of UPA mares. The proportion of pregnancies affected by UPA was 4.2 % (n=177/4192). Placental abnormality severity was scored as PSc1 (51.4 %), PSc2 (32.8 %) and PSc3 (15.8 %). The generalized mixed model revealed PSc was affected by mare age and mare status (own pregnancy (OP) or embryo transfer recipient (ER)) (P=0.035) with ER mares having increased PSc compared with mares having their own pregnancy. Abortion occurred in 17/177 (9.6 %) UPA pregnancies. Overall, at the end of the next season, 61.1 % of UPA mares were pregnant, 32.0 % barren, and 6.9 % open (n=175). Pregnancy was established in 62/91(68.1 %) of mares with PSc1, 31/58 (53.4 %) with PSc2 and 14/26 (53.8 %) with PSc3. Most pregnancies were achieved in the first 81/107 (75.7 %) or second 18/107 (16.8 %) inseminated cycle. In conclusion, early detection and treatment of ultrasonographic assessed placental abnormalities can save high-risk pregnancies in > 90 % of cases with a satisfying subsequent fertility.
ABSTRACT
SUMMARY: Out-of-hospital cardiac arrest is a serious public health problem worldwide. The annual incidence is estimated at around 400 000 cases in Europe and the United States, and survival rates scarcely reach 10%. However, there is considerable variation between countries and even between regions that share a similar health care system within a single country. Information recorded by the Out-of-Hospital Spanish Cardiac Arrest Registry (OHSCAR) provides information on care provided by emergency ambulance services, final health outcomes after cardiac arrest cases (including variations), the possibility of organ donation, and the impact of the COVID-19 pandemic. This paper presents the OHSCAR report for Spanish emergency services for the year 2022.
RESUMEN: La parada cardiorrespiratoria extrahospitalaria (PCREH) es un grave problema de salud pública mundial, con una incidencia anual estimada entorno a entorno a los 350.000 y 400.000 casos de PCERH en Europa y Estados Unidos, respectivamente. La supervivencia final se sitúa en porcentajes que apenas alcanzan el 10%, aunque existe una importante variabilidad entre países e incluso entre regiones del mismo país con modelos de atención similares. En España, el Registro Español de Parada Cardiaca Extrahospitalaria (acrónimo OHSCAR) ha ofrecido información sobre la asistencia a la PCRE prestada por los servicios de emergencias (SEM) y sus resultados finales en salud, así como sobre variabilidad, posibilidades de programas de donación o impacto de la pandemia COVID-19. A continuación se presenta el informe OHSCAR correspondiente a la asistencia a la PCRE por los SEM españoles durante el año 2022.
Subject(s)
Cardiopulmonary Resuscitation , Out-of-Hospital Cardiac Arrest , Humans , United States , Out-of-Hospital Cardiac Arrest/epidemiology , Out-of-Hospital Cardiac Arrest/therapy , Incidence , Pandemics , Registries , HospitalsABSTRACT
Hibernation is a widespread metabolic strategy among mammals for surviving periods of food scarcity. During hibernation, animals naturally alternate between metabolically depressed torpor bouts and energetically expensive arousals without ill effects. As a result, hibernators are promising models for investigating mechanisms that buffer against cellular stress, including telomere protection and restoration. In non-hibernators, telomeres, the protective structural ends of chromosomes, shorten with age and metabolic stress. In temperate hibernators, however, telomere shortening and elongation can occur in response to changing environmental conditions and associated metabolic state. We investigate telomere dynamics in a tropical hibernating primate, the fat-tailed dwarf lemur (Cheirogaleus medius). In captivity, these lemurs can hibernate when maintained under cold temperatures (11-15 °C) with limited food provisioning. We study telomere dynamics in eight fat-tailed dwarf lemurs at the Duke Lemur Center, USA, from samples collected before, during, and after the hibernation season and assayed via qPCR. Contrary to our predictions, we found that telomeres were maintained or even lengthened during hibernation, but shortened immediately thereafter. During hibernation, telomere lengthening was negatively correlated with time in euthermia. Although preliminary in scope, our findings suggest that there may be a preemptive, compensatory mechanism to maintain telomere integrity in dwarf lemurs during hibernation. Nevertheless, telomere shortening immediately afterward may broadly result in similar outcomes across seasons. Future studies could profitably investigate the mechanisms that offset telomere shortening within and outside of the hibernation season and whether those mechanisms are modulated by energy surplus or crises.
Subject(s)
Cheirogaleidae , Hibernation , Telomere , Animals , Hibernation/physiology , Cheirogaleidae/physiology , Cheirogaleidae/genetics , Male , Female , Telomere Homeostasis/physiology , Telomere Shortening/physiology , SeasonsABSTRACT
With the aim of helping researchers to develop intelligent operation and maintenance strategies, in this manuscript, an extensive 3-years Supervisory Control and Data Acquisition database of five Fuhrländer FL2500 2.5 MW wind turbines is presented. The database contains 312 analogous variables recorded at 5-minute intervals, from 78 different sensors. The reported values for each sensor are minimum, maximum, mean, and standard deviation. The database also contains the alarm events, indicating the system and subsystem and a small description. Finally, a set of functions to download specific subsets of the whole database is freely available in Matlab, R, and Python. To demonstrate the usefulness of this database, an illustrative example is given. In this example, different gearbox variables are selected to estimate a target variable to detect whether or not the estimate differs from the actual value provided for the sensor. By using this normality modelling approach, it is possible to detect rotor malfunction when the estimate differs from the actual measured value.
ABSTRACT
Despite our increasing knowledge of molecular mechanisms guiding various aspects of human reproduction, those underlying human primordial germ cell (PGC) development remain largely unknown. Here, we conducted custom CRISPR screening in an in vitro system of human PGC-like cells (hPGCLCs) to identify genes required for acquisition and maintenance of PGC fate. Amongst our candidates, we identified TCL1A, an AKT coactivator. Functional assessment in our in vitro hPGCLCs system revealed that TCL1A played a critical role in later stages of hPGCLC development. Moreover, we found that TCL1A loss reduced AKT-mTOR signaling, downregulated expression of genes related to translational control, and subsequently led to a reduction in global protein synthesis and proliferation. Together, our study highlights the utility of CRISPR screening for human in vitro-derived germ cells and identifies novel translational regulators critical for hPGCLC development.
Subject(s)
Clustered Regularly Interspaced Short Palindromic Repeats , Proto-Oncogene Proteins c-akt , Humans , Clustered Regularly Interspaced Short Palindromic Repeats/genetics , Proto-Oncogene Proteins c-akt/metabolism , Cell Differentiation/genetics , Germ Cells/metabolism , TranscriptomeABSTRACT
INTRODUCTION: Headache is a frequent symptom at the acute phase of coronavirus disease 2019 (COVID-19) and also one of the most frequent adverse effects following vaccination. In both cases, headache pathophysiology seems linked to the host immune response and could have similarities. We aimed to compare the clinical phenotype and the frequency and associated onset symptoms in patients with COVID-19 related-headache and COVID-19 vaccine related-headache. SUBJECTS AND METHODS: A case-control study was conducted. Patients with confirmed COVID-19 infection and COVID-19-vaccine recipients who experienced new-onset headache were included. A standardised questionnaire was administered, including demographic variables, prior history of headaches, associated symptoms and headache-related variables. Both groups were matched for age, sex, and prior history of headache. A multivariate regression analysis was performed. RESULTS: A total of 238 patients fulfilled eligibility criteria (143 patients with COVID-19 related-headache and 95 subjects experiencing COVID-19 vaccine related-headache). Patients with COVID-19 related-headache exhibited a higher frequency of arthralgia, diarrhoea, dyspnoea, chest pain, expectoration, anosmia, myalgia, odynophagia, rhinorrhoea, cough, and dysgeusia. Further, patients with COVID-19 related-headache had a more prolonged daily duration of headache and described the headache as the worst headache ever experienced. Patients with COVID-19 vaccine-related headache, experienced more frequently pain in the parietal region, phonophobia, and worsening of the headache by head movements or eye movements. CONCLUSION: Headache caused by SARS-CoV-2 infection and COVID-19 vaccination related-headache have more similarities than differences, supporting a shared pathophysiology, and the activation of the innate immune response. The main differences were related to associated symptoms.
TITLE: Diferencias y similitudes entre la cefalea relacionada con la COVID-19 y la cefalea relacionada con la vacuna de la COVID-19. Un estudio de casos y controles.Introducción. La cefalea es un síntoma frecuente en la fase aguda de la enfermedad por coronavirus 2019 (COVID-19) y también uno de los efectos adversos más comunes tras la vacunación. En ambos casos, la fisiopatología de la cefalea parece estar relacionada con la respuesta inmunitaria del huésped y podría presentar similitudes. Nuestro objetivo fue comparar el fenotipo clínico y la frecuencia de los síntomas asociados y los síntomas de inicio en pacientes con cefalea relacionada con la COVID-19 y cefalea relacionada con la vacuna de la COVID-19. Sujetos y métodos. Se realizó un estudio de casos y controles. Se incluyó a pacientes con infección confirmada por COVID-19 y receptores de la vacuna de la COVID-19 que experimentaron un nuevo inicio de cefalea. Se administró un cuestionario estandarizado que incluyó variables demográficas, antecedentes previos de cefaleas, síntomas asociados y variables relacionadas con la cefalea. Ambos grupos se emparejaron por edad, sexo y antecedentes previos de cefaleas. Se realizó un análisis de regresión multivariante. Resultados. Un total de 238 pacientes cumplieron con los criterios de elegibilidad (143 pacientes con cefalea relacionada con la COVID-19 y 95 sujetos con cefalea relacionada con la vacuna de la COVID-19). Los pacientes con cefalea relacionada con la COVID-19 presentaron una mayor frecuencia de artralgia, diarrea, disnea, dolor torácico, expectoración, anosmia, mialgia, odinofagia, rinorrea, tos y disgeusia. Además, los pacientes con cefalea relacionada con la COVID-19 experimentaron una duración diaria más prolongada de la cefalea y describieron la cefalea como la peor que habían experimentado. Los pacientes con cefalea relacionada con la vacuna de la COVID-19 experimentaron con más frecuencia dolor en la región parietal, fonofobia y empeoramiento de la cefalea por movimientos de la cabeza o de los ojos. Conclusión. La cefalea causada por la infección por el SARS-CoV-2 y la cefalea relacionada con la vacunación de la COVID-19 presentan más similitudes que diferencias, lo que respalda una fisiopatología compartida y la activación de la respuesta inmunitaria innata. Las principales diferencias estuvieron relacionadas con los síntomas asociados.
Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , COVID-19 Vaccines/adverse effects , COVID-19/complications , Case-Control Studies , SARS-CoV-2 , Headache/chemically induced , Headache/epidemiology , Chest PainABSTRACT
Introduction: The multiple forced expiratory maneuvers that must be performed during methacholine test require a high degree of collaboration and can lead to fatigue. However, impulse oscillometry (IOS) is a noninvasive test, quick and easy to perform, that does not require effort-dependent maneuvers.Objectives: The primary endpoint was to evaluate the relationship between IOS and spirometry during the methacholine test. The secondary endpoint was to study the predictive value of baseline IOS in the development of bronchial hyperreactivity.Methods: Observational, prospective, cross-sectional study, with recruitment of consecutive patients from the pulmonology department with clinical suspicion of bronchial asthma with negative bronchodilator test and normal FeNO.Results: Twenty-five patients were included, with a mean age of 49 ± 18 years. Thirteen patients (52%) had a positive methacholine test. The correlation between IOS indices and FEV1 was significant (p < 0.05) in all cases. The indices with the highest predictive power were R5-20 and AX. The optimal cutoff points were an increase of greater than 32.96% in R5, greater than 120.83% for X5, an increase of 30.30 [kPa l-1s-1] in R5-20, and an increase of 1.01 [kPa l-1] for AX. Baseline oscillometry demonstrated a strong predictive value in the development of bronchial hyperreactivity, with a sensitivity of 61.5% and a specificity of 91.7%, using the cut-off point of 160.0% for R5.Conclusions: IOS may be a valuable alternative to forced spirometry in detecting bronchial hyperreactivity during the methacholine test, showing a good correlation between both tests.
ABSTRACT
OBJECTIVE: Colorectal cancer (CRC) is a leading cause of cancer-related deaths, with the majority of cases initiated by inactivation of the APC tumour suppressor. This results in the constitutive activation of canonical WNT pathway transcriptional effector ß-catenin, along with induction of WNT feedback inhibitors, including the extracellular palmitoleoyl-protein carboxylesterase NOTUM which antagonises WNT-FZD receptor-ligand interactions. Here, we sought to evaluate the effects of NOTUM activity on CRC as a function of driver mutation landscape. DESIGN: Mouse and human colon organoids engineered with combinations of CRC driver mutations were used for Notum genetic gain-of-function and loss-of-function studies. In vitro assays, in vivo endoscope-guided orthotopic organoid implantation assays and transcriptomic profiling were employed to characterise the effects of Notum activity. Small molecule inhibitors of Notum activity were used in preclinical therapeutic proof-of-principle studies targeting oncogenic Notum activity. RESULTS: NOTUM retains tumour suppressive activity in APC-null adenomas despite constitutive ß-catenin activity. Strikingly, on progression to adenocarcinoma with P53 loss, NOTUM becomes an obligate oncogene. These phenotypes are Wnt-independent, resulting from differential activity of NOTUM on glypican 1 and 4 in early-stage versus late-stage disease, respectively. Ultimately, preclinical mouse models and human organoid cultures demonstrate that pharmacological inhibition of NOTUM is highly effective in arresting primary adenocarcinoma growth and inhibiting metastatic colonisation of distal organs. CONCLUSIONS: Our findings that a single agent targeting the extracellular enzyme NOTUM is effective in treating highly aggressive, metastatic adenocarcinomas in preclinical mouse models and human organoids make NOTUM and its glypican targets therapeutic vulnerabilities in advanced CRC.
Subject(s)
Adenocarcinoma , Colorectal Neoplasms , Humans , Mice , Animals , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Mutation , Wnt Signaling Pathway/genetics , Catenins/genetics , Catenins/metabolism , Catenins/pharmacology , Adenocarcinoma/drug therapy , Adenocarcinoma/geneticsABSTRACT
BACKGROUND: In myelodysplastic neoplasms (MDS), the 20q deletion [del(20q)] is a recurrent chromosomal abnormality that it has a high co-occurrence with U2AF1 mutations. Nevertheless, the prognostic impact of U2AF1 in these MDS patients is uncertain and the possible clinical and/or prognostic differences between the mutation type and the mutational burden are also unknown. METHODS: Our study analyzes different molecular variables in 100 MDS patients with isolated del(20q). RESULTS & CONCLUSIONS: We describe the high incidence and negative prognostic impact of U2AF1 mutations and other alterations such as in ASXL1 gene to identify prognostic markers that would benefit patients to receive earlier treatment.
Subject(s)
Myelodysplastic Syndromes , Splicing Factor U2AF , Humans , Incidence , Mutation , Myelodysplastic Syndromes/epidemiology , Myelodysplastic Syndromes/genetics , Prognosis , Splicing Factor U2AF/geneticsABSTRACT
Proanthocyanidins (PAC) can modulate the fatty acid (FA) profile of animal products and make them healthier for human consumption, but their effects are highly variable depending on several factors such as PAC chemical structure or dose. The present experiment aimed to evaluate the effect of PAC on the milk FA profile of Rasa Aragonesa ewes fed fresh sainfoin (PAC-containing forage legume) during the rearing period of suckling lambs (4 weeks postlambing). Twenty lactating ewes rearing a single male lamb were fed fresh sainfoin ad libitum plus 200 g/d of barley. Half the ewes were orally dosed with 100 mL of water (Sainfoin Group; n = 10) and the other half with polyethylene glycol (50 g PEG4000/100 mL water, Sainfoin + PEG Group; n = 10) to block PAC effects. Sainfoin and milk samples were collected weekly to determine their FA profile by gas chromatography. Fresh sainfoin contents of C18:3n-3 decreased from week 1 to week 2, C16:0 and C18:0 increased from week 1 to week 3, and C18:2n-6 did not change. Regarding milk FA, there were minor effects of PAC on milk-saturated FA. During the whole study, the presence of PAC increased C18:0, C18:2n-6, C18:3n-3 and total polyunsaturated FA (PUFA) n-6 and n-3, and decreased C18:1 t11, branched- and odd-chain FA. However, the decrease of milk concentrations of trans-monounsaturated FA, C18:1 t10, and total conjugated linoleic acid (CLA) and the increase of total PUFA due to the presence of PAC occurred only in week 1, while CLA c9,t11 was lower during weeks 1 and 2. The canonical analyses confirmed the differences between treatments in the FA profile of milk. Overall, the use of fresh sainfoin in the diet of lactating ewes resulted in a beneficial modification of the concentration of several milk FAs, suggesting some changes in ruminal biohydrogenation.
Subject(s)
Linoleic Acids, Conjugated , Proanthocyanidins , Sheep , Animals , Female , Male , Humans , Fatty Acids/analysis , Milk/chemistry , Lactation , Proanthocyanidins/pharmacology , Diet/veterinary , Fatty Acids, Unsaturated/analysis , Sheep, Domestic , Animal Feed/analysis , Dietary Supplements , Linoleic Acids, Conjugated/pharmacologyABSTRACT
Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS.
Subject(s)
Carcinoid Tumor , Neuroendocrine Tumors , Humans , B7-H1 Antigen , LungABSTRACT
KEY MESSAGE: We documented changes in the wheat genome attributed to genomic selection including loss of diversity, and changes in population structure and linkage disequilibrium patterns. We conclude that training and prediction populations need to co-evolve instead of the use of a static training population. Genomic selection (GS) is widely used in plant breeding to shorten breeding cycles. Our objective was to assess the impact of rapid cycling GS on the wheat genome. We used 3927 markers to genotype a training population (YTP) and individuals from five cycles (YC1-YC5) of GS for grain yield. We assessed changes of allele frequency, genetic distance, population structure, and linkage disequilibrium (LD). We found 27.3% of all markers had a significant allele frequency change by YC5, 18% experienced a significant change attributed to selection, and 9.3% had a significant change due to either drift or selection. A total of 725 of 3927 markers were fixed by YC5 with selection fixing 7.3% of the 725 markers. The genetic distance between cycles increased over time. The Fst value of 0.224 between YTP and YC5 indicates their relationship was low. The number LD blocks decreased over time and the correlation between LD matrices also decreased over time. Overall, we found a reduction in genetic diversity, increased genetic differentiation of cycles from the training population, and restructuring of the LD patterns over cycles. The accuracy of GS depends on the genomic similarity of the training population and the prediction populations. Our results show that the similarity can decline rapidly over cycles of GS and compromise the predictive ability of the YTP-based model. Our results support implementing a GS scheme where the training and prediction populations co-evolve instead of the use of a static training population.
Subject(s)
Selection, Genetic , Triticum , Humans , Triticum/genetics , Phenotype , Plant Breeding/methods , Genotype , Genomics/methods , Genome, Plant , Models, Genetic , Polymorphism, Single NucleotideABSTRACT
Fragility of regulatory T (Treg) cells manifested by the loss of neuropilin-1 (NRP1) and expression of IFNγ undermines the immune suppressive functions of Treg cells and contributes to the success of immune therapies against cancers. Intratumoral Treg cells somehow avoid fragility; however, the mechanisms by which Treg cells are protected from fragility in the tumor microenvironment are not well understood. Here, we demonstrate that the IFNAR1 chain of the type I IFN (IFN1) receptor was downregulated on intratumoral Treg cells. Downregulation of IFNAR1 mediated by p38α kinase protected Treg cells from fragility and maintained NRP1 levels, which were decreased in response to IFN1. Genetic or pharmacologic inactivation of p38α and stabilization of IFNAR1 in Treg cells induced fragility and inhibited their immune suppressive and protumorigenic activities. The inhibitor of sumoylation TAK981 (Subasumstat) upregulated IFNAR1, eliciting Treg fragility and inhibiting tumor growth in an IFNAR1-dependent manner. These findings describe a mechanism by which intratumoral Treg cells retain immunosuppressive activities and suggest therapeutic approaches for inducing Treg fragility and increasing the efficacy of immunotherapies.
Subject(s)
Neoplasms , T-Lymphocytes, Regulatory , Humans , Tumor Microenvironment , Neuropilin-1 , ImmunotherapyABSTRACT
Although dual-energy CT was initially described by Hounsfield in 1973, it remains underused in clinical practice. It is therefore important to emphasize the clinical benefits and limitations of this technique. Iodine mapping makes it possible to quantify the uptake of iodine, which is very important in characterizing tumors, lung perfusion, pulmonary nodules, and the tumor response to new treatments. Dual-energy CT also makes it possible to obtain virtual single-energy images and virtual images without iodinated contrast or without calcium, as well as to separate materials such as uric acid or fat and to elaborate hepatic iron overload maps. In this article, we review some of the clinical benefits and technical limitations to improve understanding of dual-energy CT and expand its use in clinical practice.
Subject(s)
Iodine , Tomography, X-Ray Computed , Calcium , Contrast Media , Tomography, X-Ray Computed/methods , Uric AcidABSTRACT
Short-term nutrient restrictions can occur naturally in extensive beef cattle production systems due to low feed quality or availability. The aims of the study were to (1) model the curves of milk yield, plasma non-esterified fatty acids (NEFAs) and ß-hydroxybutyrate (BHB) contents of beef cows in response to short nutritional challenges throughout lactation; (2) identify clusters of cows with different response profiles; (3) quantify differences in cows' response between the clusters and lactation stages. Data of BW, body condition score (BCS), milk yield, NEFA, and BHB plasma concentration from 31 adult beef cows (626 ± 48 kg at calving) were used to study the effect of 4-day feed restriction repeated over months 2, 3 and 4 of lactation. On each month, all cows received a single diet calculated to meet the requirements of the average cow: 100 % requirements for 4 days (d-4 to d-1, basal period), 55 % requirements on the next 4 days (d0 to d3, restriction period) and 100 % requirements for 4 days (d4 to d7, refeeding period). Natural cubic splines were used to model the response of milk yield, NEFA and BHB to restriction and refeeding in the 3 months. The new response variables [baseline value, peak value, days to peak and to regain baseline, and areas under the curve (AUC) during restriction and refeeding] were used to cluster cows according to their metabolic response (MR) into two groups: Low MR and High MR. The month of lactation affected all the traits, and basal values decreased as lactation advanced. Cows from both clusters had similar BW and BCS values, but those in the High MR cluster had higher basal milk yield, NEFA and BHB contents, and responded more intensely to restriction, with more marked peaks and AUCs. Reaction times were similar, and baseline values recovered during refeeding in both clusters. Our results suggest that the response was driven by cows' milk potential rather than size or body reserves, and despite high-responding cattle's higher milk yield, they were able to activate metabolic pathways to respond to and recover from the challenge.
Subject(s)
Fatty Acids, Nonesterified , Lactation , 3-Hydroxybutyric Acid , Animals , Cattle , Diet/veterinary , Energy Metabolism/physiology , Female , Lactation/physiology , Milk/metabolism , NutrientsABSTRACT
OBJECTIVES: To examine gender-related differences in the management and survival of out-of-hospital cardiac arrest (OHCA) in Spain during 2 time series. MATERIAL AND METHODS: Analysis of data recorded in the prospective Spanish OHCA registry (OHSCAR in its Spanish acronym) for 2 time series (2013-2014 and 2017-2018). We included all 11 036 consecutive cases in which an emergency team intervened. The dependent variables were arrival at the hospital after return of spontaneous circulation, overall survival to discharge, and overall survival with good neurological outcomes. Sex was the independent variable. We report descriptive statistics, patient group comparisons, and changes over time. RESULTS: Women were significantly older and less likely to experience an OHCA in a public place, receive automatic external defibrillation, have a shockable heart rhythm, and be attended by an ambulance team within 15 minutes. In addition, fewer women underwent percutaneous coronary interventions or received treatment for hypothermia on admission to the hospital. In 2013-2014 and 2017-2018, respectively, the likelihood of survival was lower for women than men on admission (odds ratio [OR], 0.52 vs OR, 0.61; P .001 and P = .009 in the 2 time series) and at discharge (OR, 0.69 vs 0.72 for men; P = .001 in both time series). Survival with good neurological outcomes was also less likely in women (OR, 0.50 vs 0.63; P .001 in both series). CONCLUSION: The odds for survival and survival with good neurological outcomes were lower for women in nearly all patient groups in both time series. These findings suggest the need to adopt new approaches to address gender differences in OHCA.
OBJETIVO: Examinar las diferencias de género en las características de la parada cardiaca extrahospitalaria (PCRE), los tratamientos, la supervivencia, y los cambios evolutivos en España. METODO: Datos de dos series temporales (2013/2014 y 2017/2018) del registro prospectivo de PCRE (OHSCAR). Se incluyeron todos los casos consecutivos en los que intervino un equipo de emergencias. Las variables dependientes fueron las variables de atención de la PCRE, la llegada al hospital con pulso espontáneo, la supervivencia global al alta, y con buenos resultados neurológicos. El sexo fue la variable independiente. RESULTADOS: Las mujeres fueron significativamente mayores, menos propensas a presentar una PCRE en lugar público, recibir desfibrilación externa automática, tener un ritmo inicial desfibrilable y ser atendidas por una ambulancia en menos de 15 minutos. Además, menos mujeres recibieron intervención coronaria percutánea o hipotermia al ingreso hospitalario. Tanto en 2013/2014 como en 2017/2018 las mujeres tuvieron menos probabilidades de supervivencia al ingreso hospitalario (OR = 0,52; p 0,001; OR = 0,61; p = 0,009 respectivamente), y al alta hospitalaria (OR = 0,69; p = 0,001; OR = 0,72; p = 0,001, respectivamente) y con buenos resultados neurológicos (OR = 0,50; p 0,001; OR = 0,63; p 0,001, respectivamente). CONCLUSIONES: En ambos periodos las mujeres tuvieron menos probabilidades de sobrevivir y de hacerlo en buenas condiciones neurológicas. Estos resultados indican la necesidad de adoptar nuevos enfoques para abordar las diferencias de género en la PCRE.