RESUMO
Cellular senescence is a cell fate triggered in response to stress and is characterized by stable cell-cycle arrest and a hypersecretory state. It has diverse biological roles, ranging from tissue repair to chronic disease. The development of new tools to study senescence in vivo has paved the way for uncovering its physiological and pathological roles and testing senescent cells as a therapeutic target. However, the lack of specific and broadly applicable markers makes it difficult to identify and characterize senescent cells in tissues and living organisms. To address this, we provide practical guidelines called "minimum information for cellular senescence experimentation in vivo" (MICSE). It presents an overview of senescence markers in rodent tissues, transgenic models, non-mammalian systems, human tissues, and tumors and their use in the identification and specification of senescent cells. These guidelines provide a uniform, state-of-the-art, and accessible toolset to improve our understanding of cellular senescence in vivo.
Assuntos
Senescência Celular , Humanos , Animais , Biomarcadores/metabolismo , Guias como Assunto , Neoplasias/patologiaRESUMO
Inhibition of the electron transport chain (ETC) prevents the regeneration of mitochondrial NAD+, resulting in cessation of the oxidative tricarboxylic acid (TCA) cycle and a consequent dependence upon reductive carboxylation for aspartate synthesis. NAD+ regeneration alone in the cytosol can rescue the viability of ETC-deficient cells. Yet, how this occurs and whether transfer of oxidative equivalents to the mitochondrion is required remain unknown. Here, we show that inhibition of the ETC drives reversal of the mitochondrial aspartate transaminase (GOT2) as well as malate and succinate dehydrogenases (MDH2 and SDH) to transfer oxidative NAD+ equivalents into the mitochondrion. This supports the NAD+-dependent activity of the mitochondrial glutamate dehydrogenase (GDH) and thereby enables anaplerosis-the entry of glutamine-derived carbon into the TCA cycle and connected biosynthetic pathways. Thus, under impaired ETC function, the cytosolic redox state is communicated into the mitochondrion and acts as a rheostat to support GDH activity and cell viability.
Assuntos
Malato Desidrogenase , NAD , NAD/metabolismo , Malato Desidrogenase/genética , Malato Desidrogenase/metabolismo , Oxirredução , Ciclo do Ácido Cítrico/fisiologia , RespiraçãoRESUMO
During oncogene-induced senescence (OIS), heterochromatin is lost from the nuclear periphery and forms internal senescence-associated heterochromatin foci (SAHFs). We show that an increased nuclear pore density during OIS is responsible for SAHF formation. In particular, the nucleoporin TPR is necessary for both formation and maintenance of SAHFs. Loss of SAHFs does not affect cell cycle arrest but abrogates the senescence-associated secretory phenotype-a program of inflammatory cytokine gene activation. Our results uncover a previously unknown role of nuclear pores in heterochromatin reorganization in mammalian nuclei and demonstrate the importance of heterochromatin organization for a specific gene activation program.
Assuntos
Senescência Celular/fisiologia , Heterocromatina/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Poro Nuclear/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Linhagem Celular , Núcleo Celular/metabolismo , Técnicas de Silenciamento de Genes , Heterocromatina/genética , Humanos , Modelos Moleculares , Poro Nuclear/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Proteínas Proto-Oncogênicas/genética , RNA Interferente Pequeno/metabolismo , Ativação Transcricional/genéticaRESUMO
AIMS: Slow conduction (SC) anatomical isthmuses (AIs) are the dominant substrate for monomorphic ventricular tachycardia (VT) in patients with repaired tetralogy of Fallot (rTF). This study aimed to evaluate the utility of automated propagational analysis for the identification of SC-AI in patients with rTF. METHODS AND RESULTS: Consecutive rTF patients undergoing VT substrate characterization were included. Automated isochronal late activation maps (ILAM) were obtained with multielectrode HD Grid Catheter. Identified deceleration zones (DZs) were compared with both SC-AI defined by conduction velocity (CV) (<0.5â m/s) and isthmuses of induced VT for mechanistic correlation. Fourteen patients were included (age 48; p25-75 35-52 years; 57% male), 2 with spontaneous VT and 12 for risk stratification. Nine VTs were inducible in seven patients. Procedure time was 140 (p25-75 133-180) min and mapping time 29.5 (p25-75 20-37.7) min, using a median of 2167 points. All the patients had at least one AI by substrate mapping, identifying a total of 27 (11 SC-AIs). Isochronal late activation maps detected 10 DZs mostly in the AI between ventricular septal defect and pulmonary valve (80%). Five patients had no DZs. A significant negative correlation between number of isochrones/cm and CV was observed (rho -0.87; P < 0.001). Deceleration zones correctly identified SC-AI (90% sensitivity; 100% specificity; 0.94 accuracy) and was related to VT inducibility (P = 0.006). Deceleration zones co-localized to the critical isthmus of induced VTs in 88% of cases. No complications were observed. CONCLUSION: Deceleration zones displayed by ILAM during sinus rhythm accurately identify SC-AIs in rTF patients allowing a safe and short-time VT substrate characterization procedure.
Assuntos
Ablação por Cateter , Valva Pulmonar , Taquicardia Ventricular , Tetralogia de Fallot , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Tetralogia de Fallot/cirurgia , Frequência Cardíaca/fisiologia , Arritmias Cardíacas , Ablação por Cateter/efeitos adversosRESUMO
Ivermectin (IVM) resistance in parasitic nematodes such as Haemonchus contortus has spurred a search for substances that help to recover its efficacy. One potential agent is the natural product curcumin (CUR). In this study, CUR was combined with polyvinylpyrrolidone (PVP) (CUR/PVP) to improve its solubility and biological applicability. This study determined the effect of CUR preincubation on the effective concentration 50% (EC50) of IVM in three H. contortus isolates with different susceptibilities to IVM. The IVM EC50 was determined for three H. contortus isolates with different IVM susceptibilities using the larval migration inhibition (LMI) test. The three isolates were (i) PARAISO (IVM resistant), (ii) FMVZ-UADY (IVM susceptible), and (iii) CENID-SAI INIFAP (reference IVM susceptible). The L3 of each isolate were preincubated for 3 h with one of three concentrations of CUR (µg curcumin/mL): CONC-1 (3.67), CONC-2 (5.67), or CONC-3 (8.48). Corresponding controls were performed without CUR. The EC50 of IVM was determined for each isolate after they were exposed to the different CUR concentrations. The EC50 of IVM differed between the isolates PARAISO > FMVZ-UADY > CENID-SAI INIFAP (P < 0.05). The CUR preincubation at CONC-1 did not decrease the EC50 of IVM for any of the three isolates, suggesting a hormetic effect. By contrast, CUR preincubation at CONC-2 or CONC-3 decreased the IVM EC50 for the PARAISO isolate (P < 0.05) compared with the reference isolate and reduced the EC50 of IVM for the FMVZ-UADY and CENID-SAI INIFAP isolates below the EC50 for the CENID-SAI INIFAP isolate without CUR preincubation. In conclusion, preincubation of H. contortus L3 with CUR reduced the EC50 of IVM for field isolates classified as resistant and susceptible to IVM. The CUR preincubation reduced the IVM resistance factor in the different isolates tested.
Assuntos
Anti-Helmínticos , Curcumina , Hemoncose , Haemonchus , Animais , Ivermectina/farmacologia , Ivermectina/uso terapêutico , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Curcumina/farmacologia , Curcumina/uso terapêutico , Povidona/farmacologia , Povidona/uso terapêutico , Resistência a Medicamentos , Larva , Hemoncose/tratamento farmacológico , Hemoncose/veterináriaRESUMO
Explanations for differences in thermal biology within and between species of lizards employ concepts of phylogenetic inertia and plasticity. We compared the thermal biology of three liolaemid species in the Andean highlands in Argentina: two allopatric congeners (Phymaturus williamsi and P. aguanegra) each in syntopy with Liolaemus parvus. We predicted intra and inter-generic differences in ecophysiological traits and periods of activity at both sites, ecotypic differences between the (labile) Liolaemus populations, but predicted no interspecific differences between the (putatively conservative) Phymaturus. We determined the operative temperatures (T e), field body temperatures (T b), preferred temperatures (T pref), effectiveness of thermoregulation (E), and activity periods. As expected, P. williamsi differed from L. parvus in T b, T pref, and activity periods, likely as result of niche segregation. Contrary to predictions, the Phymaturus populations exhibited differentiation in T b and T pref, while L. parvus populations differed in T pref and E. Accordingly, Phymaturus species tend to be effective thermoregulators whereas L. parvus populations behave as good thermoregulators or thermoconformers depending on thermal conditions in fluctuating habitats. Phymaturus may be less evolutionarily conservative than previously suggested. The suite of co-evolving traits affecting thermal ecology may not be collectively conservative nor labile but rather a continuum between both evolutionary paths.
Assuntos
Lagartos , Animais , Argentina , Filogenia , Temperatura Corporal , TemperaturaRESUMO
Chromosomal instability is a hallmark of cancer, but mitotic regulators are rarely mutated in tumors. Mutations in the condensin complexes, which restructure chromosomes to facilitate segregation during mitosis, are significantly enriched in cancer genomes, but experimental evidence implicating condensin dysfunction in tumorigenesis is lacking. We report that mice inheriting missense mutations in a condensin II subunit (Caph2nes) develop T-cell lymphoma. Before tumors develop, we found that the same Caph2 mutation impairs ploidy maintenance to a different extent in different hematopoietic cell types, with ploidy most severely perturbed at the CD4+CD8+ T-cell stage from which tumors initiate. Premalignant CD4+CD8+ T cells show persistent catenations during chromosome segregation, triggering DNA damage in diploid daughter cells and elevated ploidy. Genome sequencing revealed that Caph2 single-mutant tumors are near diploid but carry deletions spanning tumor suppressor genes, whereas P53 inactivation allowed Caph2 mutant cells with whole-chromosome gains and structural rearrangements to form highly aggressive disease. Together, our data challenge the view that mitotic chromosome formation is an invariant process during development and provide evidence that defective mitotic chromosome structure can promote tumorigenesis.
Assuntos
Adenosina Trifosfatases/genética , Proteínas de Ligação a DNA/genética , Instabilidade Genômica/genética , Linfoma de Células T/genética , Complexos Multiproteicos/genética , Mutação de Sentido Incorreto/genética , Neoplasias do Timo/genética , Adenosina Trifosfatases/metabolismo , Anáfase , Animais , Células Cultivadas , Estruturas Cromossômicas/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Linfoma de Células T/fisiopatologia , Masculino , Metáfase , Camundongos , Complexos Multiproteicos/metabolismo , Timócitos/patologia , Neoplasias do Timo/fisiopatologiaRESUMO
With the ongoing COVID-19 (Coronavirus Disease 2019) pandemic, caused by the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), there is a need for sensitive, specific, and affordable diagnostic tests to identify infected individuals, not all of whom are symptomatic. The most sensitive test involves the detection of viral RNA using RT-qPCR (quantitative reverse transcription PCR), with many commercial kits now available for this purpose. However, these are expensive, and supply of such kits in sufficient numbers cannot always be guaranteed. We therefore developed a multiplex assay using well-established SARS-CoV-2 targets alongside a human cellular control (RPP30) and a viral spike-in control (Phocine Herpes Virus 1 [PhHV-1]), which monitor sample quality and nucleic acid extraction efficiency, respectively. Here, we establish that this test performs as well as widely used commercial assays, but at substantially reduced cost. Furthermore, we demonstrate >1,000-fold variability in material routinely collected by combined nose and throat swabbing and establish a statistically significant correlation between the detected level of human and SARS-CoV-2 nucleic acids. The inclusion of the human control probe in our assay therefore provides a quantitative measure of sample quality that could help reduce false-negative rates. We demonstrate the feasibility of establishing a robust RT-qPCR assay at approximately 10% of the cost of equivalent commercial assays, which could benefit low-resource environments and make high-volume testing affordable.
Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , RNA Viral/análise , SARS-CoV-2/isolamento & purificação , Teste para COVID-19/economia , Humanos , Reação em Cadeia da Polimerase Multiplex/economia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/economia , SARS-CoV-2/genéticaRESUMO
AIMS: The aim of our study was to analyse the response to short-coupled atrial extrastimuli to identify areas of hidden slow conduction (HSC) and their relationship with the atrial fibrillation (AF) phenotype. METHODS AND RESULTS: Twenty consecutive patients with paroxysmal AF and persistent AF (10:10) underwent the first pulmonary vein isolation procedure. Triple short-coupled extrastimuli were delivered in sinus rhythm (SR), and the evoked response was analysed: sites exhibiting double or highly fragmented electrograms (EGM) were defined as positive for HSC (HSC+). The delta of the duration of the bipolar EGM was analysed, and bipolar EGM duration maps were built. High-density maps were acquired using a multipolar catheter during AF, SR, and paced rhythm. Spatial co-localization of HSC+ and complex fractionated atrial EGMs (CFAE) during AF was evaluated. Persistent AF showed a higher number and percentage of HSC+ than paroxysmal AF (13.9% vs. 3.3%, P < 0.001). The delta of EGM duration was 53 ± 22â ms for HSC+ compared with 13 ± 11 (10)â ms in sites with negative HSC (HSC-) (P < 0.001). The number and density of HSC+ were lower than CFAE during AF (19 vs. 56 per map, P < 0.001). The reproducibility and distribution of HSC+ in repeated maps were superior to CFAE (P = 0.19 vs. P < 0.001). Sites with negative and positive responses showed a similar bipolar voltage in the preceding sinus beat (1.65 ± 1.34 and 1.48 ± 1.47â mV, P = 0.12). CONCLUSION: Functional mapping identifies more discrete and reproducible abnormal substrates than mapping during AF. The HSC+ sites in response to triple extrastimuli are more frequent in persistent AF than in paroxysmal AF.
Assuntos
Fibrilação Atrial , Ablação por Cateter , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Reprodutibilidade dos Testes , Técnicas Eletrofisiológicas Cardíacas/métodos , Frequência Cardíaca , Átrios do CoraçãoRESUMO
AIMS: Electrical cardioversion is commonly used to restore sinus rhythm in patients with atrial fibrillation (AF), but procedural technique and clinical success vary. We sought to identify techniques associated with electrical cardioversion success for AF patients. METHODS AND RESULTS: We searched MEDLINE, EMBASE, CENTRAL, and the grey literature from inception to October 2022. We abstracted data on initial and cumulative cardioversion success. We pooled data using random-effects models. From 15 207 citations, we identified 45 randomized trials and 16 observational studies. In randomized trials, biphasic when compared with monophasic waveforms resulted in higher rates of initial [16 trials, risk ratio (RR) 1.71, 95% CI 1.29-2.28] and cumulative success (18 trials, RR 1.10, 95% CI 1.04-1.16). Fixed, high-energy (≥200 J) shocks when compared with escalating energy resulted in a higher rate of initial success (four trials, RR 1.62, 95% CI 1.33-1.98). Manual pressure when compared with no pressure resulted in higher rates of initial (two trials, RR 2.19, 95% CI 1.21-3.95) and cumulative success (two trials, RR 1.19, 95% CI 1.06-1.34). Cardioversion success did not differ significantly for other interventions, including: antero-apical/lateral vs. antero-posterior positioned pads (initial: 11 trials, RR 1.16, 95% CI 0.97-1.39; cumulative: 14 trials, RR 1.01, 95% CI 0.96-1.06); rectilinear/pulsed biphasic vs. biphasic truncated exponential waveform (initial: four trials, RR 1.11, 95% CI 0.91-1.34; cumulative: four trials, RR 0.98, 95% CI 0.89-1.08) and cathodal vs. anodal configuration (cumulative: two trials, RR 0.99, 95% CI 0.92-1.07). CONCLUSIONS: Biphasic waveforms, high-energy shocks, and manual pressure increase the success of electrical cardioversion for AF. Other interventions, especially pad positioning, require further study.
Assuntos
Fibrilação Atrial , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/terapia , Cardioversão Elétrica/efeitos adversos , Cardioversão Elétrica/métodos , Eletrodos , Resultado do TratamentoRESUMO
Cells enter senescence, a state of stable proliferative arrest, in response to a variety of cellular stresses, including telomere erosion, DNA damage, and oncogenic signaling, which acts as a barrier against malignant transformation in vivo. To identify genes controlling senescence, we conducted an unbiased screen for small hairpin RNAs that extend the life span of primary human fibroblasts. Here, we report that knocking down the chemokine receptor CXCR2 (IL8RB) alleviates both replicative and oncogene-induced senescence (OIS) and diminishes the DNA-damage response. Conversely, ectopic expression of CXCR2 results in premature senescence via a p53-dependent mechanism. Cells undergoing OIS secrete multiple CXCR2-binding chemokines in a program that is regulated by the NF-kappaB and C/EBPbeta transcription factors and coordinately induce CXCR2 expression. CXCR2 upregulation is also observed in preneoplastic lesions in vivo. These results suggest that senescent cells activate a self-amplifying secretory network in which CXCR2-binding chemokines reinforce growth arrest.
Assuntos
Senescência Celular , Receptores de Interleucina-8B/genética , Receptores de Interleucina-8B/metabolismo , Transdução de Sinais , Adenocarcinoma/metabolismo , Animais , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Quimiocinas/metabolismo , Dano ao DNA , Regulação para Baixo , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Ligantes , Neoplasias Pulmonares/metabolismo , Camundongos , NF-kappa B/metabolismo , Lesões Pré-Cancerosas/metabolismo , Interferência de RNA , Receptores de Interleucina-8A/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
This study developed and evaluated an in vitro rumen incubation (IVRI) method to describe the exsheathment kinetics of Haemonchus contortus third-stage infective larvae (L3) in ruminal liquor (RL). The specific objectives were (i) to standardize the IVRI method to facilitate the contact between L3 and RL as well as the larval recovery, and (ii) to apply the IVRI method to describe the exsheathment kinetics of H. contortus and to select the best fitting nonlinear model. Incubation devices containing H. contortus larvae were incubated according to the IVRI technique in cattle RL or PBS. The incubation conditions included RL mixed with a nitrogen-rich media, maintained at 39 °C, with pH = 7.0, vented with CO2 and manual agitation. The larvae were recovered after 0, 1, 3, 6, 9, 12, and 24 h. The exsheathed and ensheathed larvae were counted to estimate the exsheathment (%) in RL or PBS. Exsheathment in RL was analyzed with nonlinear regression models: Exponential, Gompertz, Logistic, Log-Logistic, and Weibull. The models' fit was compared to select the one that best described the exsheathment kinetics. The exsheathment in RL reached 6.52%, 20.65%, 58.22%, 69.24%, 73.08%, and 77.20% in 1, 3, 6, 9, 12, and 24 h, respectively. Although the Gompertz, Weibull, and Logistic models were adequate to describe the observed exsheathment, the Log-Logistic model had the best fit. The IVRI method using bovine RL represents a suitable tool for the study of the in vitro exsheathment kinetics of H. contortus L3.
Assuntos
Haemonchus , Animais , Bovinos , Larva , Cinética , Rúmen , Técnicas In VitroRESUMO
Several human disturbances contribute to the decrease of vertebrate species' richness and abundance, altering the processes of an ecosystem. We evaluate richness, diversity and relative abundance of species for lizard assemblages at sites with different degrees of perturbation in the center-west of the Arid Chaco region in Argentina. Between 2015 and 2018, six lizard assemblages were sampled monthly -using pitfall traps- in three areas of the Chaco, with a perturbed and an unperturbed (control) replica at each of the areas: (1) Chaco Mountain plain, (2) Chaco Mountain slope, and (3) Chaco Plains, and habitat characteristics of each study site were recorded. We captured 1446 lizards, belonging to 12 species. The perturbed area at the Chaco Mountain plain showed the greatest richness, diversity and abundance of species. In the perturbed Chaco Plains, species abundance decreased by about 50% with respect to the control site. Liolaemus chacoensis was the dominant species at all sites. Some species could be negatively affected by a total loss of arboreal strata, tree trunks and fallen leaves. Structural parameters of lizard assemblages were related to the habitat characteristics; therefore, these results provide information for the conservation and management of lands and lizard assemblages in the Arid Chaco.
Assuntos
Ecossistema , Lagartos , Humanos , Animais , Argentina , Folhas de Planta , Registros , ÁrvoresRESUMO
AIM: To investigate the mucoadhesive strength and barrier effect of Esophacare® (Atika Pharma SL, Las Palmas de Gran Canaria) in an ex vivo model of gastro-oesophageal reflux. METHODS: An ex vivo evaluation through the Falling Liquide Film Technique with porcine esophagi was performed, compared to a positive control (Ziverel®; Norgine, Amsterdam), after different washing periods with saline, acidified saline (pH 1.2) and acidified saline with pepsin (2000U/mL). RESULTS: The adhesive mean strength on the oesophageal mucosa of Esophacare was 94.7 (6.0)%, compared to 27.6 (19.1)% of the positive control (p<0.05). These results were homogeneous across the different washes and throughout the tissue. The area covered by 1mL of Esophacare, and its respective persistence after washing was also assessed, yielding a mean global persistence of 74.29 (19.7)% vs. 18.9 (12.3)% for the control (p<0.05). In addition, after 30min exposure to acidified saline with pepsin, Esophacare shows a protective effect on the oesophageal mucosa, detectable histologically: preserved integrity and structure of the apical layers was observed, as well as reduced permeability to the washing solution. CONCLUSIONS: Esophacare shows an adhesive strength close to 100%, irrespective of the washing solution applied or the oesophageal region studied. Histologically, it reduces the abrasive effects of the acidic solution on the oesophageal epithelium, reducing permeability to the washing solution. The results in this ex vivo model of gastro-oesophageal reflux disease (GERD) support its therapeutic potential.
Assuntos
Esofagite Péptica , Esofagite , Refluxo Gastroesofágico , Humanos , Pepsina A/uso terapêutico , Esofagite/patologia , Refluxo Gastroesofágico/tratamento farmacológico , Concentração de Íons de HidrogênioRESUMO
From its origins in Australia, Eucalyptus grandis has spread to every continent, except Antarctica, as a wood crop. It has been cultivated and bred for over 100 yr in places such as South Africa. Unlike most annual crops and fruit trees, domestication of E. grandis is still in its infancy, representing a unique opportunity to interrogate the genomic consequences of artificial selection early in the domestication process. To determine how a century of artificial selection has changed the genome of E. grandis, we generated single nucleotide polymorphism genotypes for 1080 individuals from three advanced South African breeding programmes using the EUChip60K chip, and investigated population structure and genome-wide differentiation patterns relative to wild progenitors. Breeding and wild populations appeared genetically distinct. We found genomic evidence of evolutionary processes known to have occurred in other plant domesticates, including interspecific introgression and intraspecific infusion from wild material. Furthermore, we found genomic regions with increased linkage disequilibrium and genetic differentiation, putatively representing early soft sweeps of selection. This is, to our knowledge, the first study of genomic signatures of domestication in a timber species looking beyond the first few generations of cultivation. Our findings highlight the importance of intra- and interspecific hybridization during early domestication.
Assuntos
Domesticação , Genoma de Planta , Genômica , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único/genética , Seleção Genética , Madeira/genéticaRESUMO
AIMS: To non-invasively characterize, by means of late gadolinium enhancement cardiac magnetic resonance (LGE-CMR), scar differences, and potential variables associated with ventricular tachycardia (VT) occurrence in chronic post-myocardial infarction (MI) patients. METHODS AND RESULTS: A case-control study was designed through retrospective LGE-CMR data analysis of chronic post-MI patients (i) consecutively referred for VT substrate ablation after a first VT episode (n = 66) and (ii) from a control group (n = 84) with no arrhythmia evidence. The myocardium was characterized differentiating core, border zone (BZ), and BZ channels (BZCs) using the ADAS 3D post-processing imaging platform. Clinical and scar characteristics, including a novel parameter, the BZC mass, were compared between both groups. One hundred and fifty post-MI patients were included. Four multivariable Cox proportional hazards regression models were created for total scar mass, BZ mass, core mass, and BZC mass, adjusting them by age, sex, and left ventricular ejection fraction (LVEF). A cut-off of 5.15 g of BZC mass identified the cases with 92.4% sensitivity and 86.9% specificity [area under the ROC curve (AUC) 0.93 (0.89-0.97); P < 0.001], with a significant increase in the AUC compared to other scar parameters (P < 0.001 for all pairwise comparisons). Adding BZC mass to LVEF allowed to reclassify 33.3% of the cases and 39.3% of the controls [net reclassification improvement = 0.73 (0.71-0.74)]. CONCLUSIONS: The mass of BZC is the strongest independent variable associated with the occurrence of sustained monomorphic ventricular tachycardia in post-MI patients after adjustment for age, sex, and LVEF. Border zone channel mass measurement could permit a more accurate VT risk stratification than LVEF in chronic post-MI patients.
Assuntos
Infarto do Miocárdio , Taquicardia Ventricular , Arritmias Cardíacas/complicações , Arritmias Cardíacas/etiologia , Estudos de Casos e Controles , Cicatriz , Meios de Contraste , Gadolínio , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Estudos Retrospectivos , Volume Sistólico , Taquicardia Ventricular/diagnóstico por imagem , Taquicardia Ventricular/etiologia , Função Ventricular EsquerdaRESUMO
Reproductive biology is fundamental to understanding the ecology and evolution of lizards which, in turn, is essential for the definition of the species´ conservation status. We studied life-history traits related to the reproduction of the Phymaturus extrilidus lizard, including the male and female reproductive cycles, litter size, mean annual reproductive output, reproductive effort, sexual maturity size and sexual dimorphism, body condition, and fat body cycles. We found sexual dimorphism in size and shape, supporting the hypotheses of sexual and fecundity selection. Females exhibited biennial reproductive cycles synchronous with the annual prenuptial male cycle, adjusted for the maturation of the vitellogenic follicles of females. Females of P. extrilidus have the highest mean annual reproductive output (MARO=1.14) recorded in Phymaturus, and this is accompanied by the highest reproductive effort (C=0.28, C energetic =0.31). Births occur from late summer to early autumn. The female reproductive cycle, strictly biennial, like all species of the P. palluma group, and the vitellogenesis in particular, appear to be limited by body condition and the amount of fat body stored. This study presents the fundamental reproductive traits of P. extrilidus that can provide valuable information to be used in the evaluation of the conservation status of this species.
Assuntos
Lagartos , Animais , Feminino , Masculino , Caracteres Sexuais , Altitude , Argentina , Reprodução , BiologiaRESUMO
Functional traits are those characteristics of organisms that influence the ability of a species to develop in a habitat and persist in the face of environmental changes. The traits are often affected by a multiplicity of species-dependent and external factors. Our objective was to investigate thermal biology of Liolaemus ruibali in a high altitude cold desert at the arid Puna region, Argentina. We address the following question: do sex and seasonal variations in environmental temperature induce changes in the ecophysiological traits? We measured and compared the operative temperatures between fall and spring; and between sexes and seasons, we compared the ecophysiological traits of lizards, microenvironmental temperatures and thermoregulatory behavior. Air and operative temperatures were different between seasons. We found an effect of season-sex interaction on field body temperatures, preferred temperatures, panting threshold and thermal quality. The voluntary and critical temperatures presented seasonal variation in relation to changes in environmental temperatures, suggesting thermal acclimatization. We note behavioral changes between seasons, with the substrate being the main resource for gaining heat in spring. We conclude that Liolaemus ruibali is an efficient thermoregulator; it is a eurythermic lizard and presents phenotypic plasticity in different ecophysiological and behavioral traits induced by sex and seasonality. In addition, we predict that this population could buffer the effects of projected global warming scenarios.
Assuntos
Altitude , Regulação da Temperatura Corporal/fisiologia , Aquecimento Global , Lagartos/fisiologia , Estações do Ano , Aclimatação , Adaptação Fisiológica , Animais , Argentina , Temperatura Corporal , TemperaturaRESUMO
This systematic review was carried out in order to highlight the implementation of ozone therapy as a treatment for nocturnal tinnitus. It is important to note that ozone treatment has resolved nocturnal tinnitus with 100% efficacy in previous studies, producing in turn a symptomatic improvement in the patient. From these results, a high degree of efficacy can be inferred in overcoming nocturnal tinnitus treated with ozone therapy in patients with a severe index of perception of tinnitus.
Assuntos
Zumbido , Humanos , Zumbido/tratamento farmacológico , Zumbido/etiologia , Resultado do TratamentoRESUMO
The genetic consequences of adaptation to changing environments can be deciphered using population genomics, which may help predict species' responses to global climate change. Towards this, we used genome-wide SNP marker analysis to determine population structure and patterns of genetic differentiation in terms of neutral and adaptive genetic variation in the natural range of Eucalyptus grandis, a widely cultivated subtropical and temperate species, serving as genomic reference for the genus. We analysed introgression patterns at subchromosomal resolution using a modified ancestry mapping approach and identified provenances with extensive interspecific introgression in response to increased aridity. Furthermore, we describe potentially adaptive genetic variation as explained by environment-associated SNP markers, which also led to the discovery of what is likely a large structural variant. Finally, we show that genes linked to these markers are enriched for biotic and abiotic stress responses.