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PURPOSE: Nivolumab plus relatlimab and nivolumab plus ipilimumab have been approved for advanced melanoma on the basis of the phase II/III RELATIVITY-047 and phase III CheckMate 067 trials, respectively. As no head-to-head trial comparing these regimens exists, an indirect treatment comparison was conducted using patient-level data from each trial. METHODS: Inverse probability of treatment weighting (IPTW) adjusted for baseline characteristic differences. Minimum follow-ups (RELATIVITY-047, 33 months; CheckMate 067, 36 months) were selected to best align assessments. Outcomes included progression-free survival (PFS), confirmed objective response rate (cORR), and melanoma-specific survival (MSS) per investigator; overall survival (OS); and treatment-related adverse events (TRAEs). A Cox regression model compared PFS, OS, and MSS. A logistic regression model compared cORRs. Subgroup analyses were exploratory. RESULTS: After IPTW, key baseline characteristics were balanced for nivolumab plus relatlimab (n = 339) and nivolumab plus ipilimumab (n = 297). Nivolumab plus relatlimab demonstrated similar PFS (hazard ratio [HR], 1.08 [95% CI, 0.88 to 1.33]), cORR (odds ratio, 0.91 [95% CI, 0.73 to 1.14]), OS (HR, 0.94 [95% CI, 0.75 to 1.19]), and MSS (HR, 0.86 [95% CI, 0.67 to 1.12]) to nivolumab plus ipilimumab. Subgroup comparisons showed larger numerical differences favoring nivolumab plus ipilimumab with acral melanoma, BRAF-mutant melanoma, and lactate dehydrogenase >2 × upper limit of normal, but were limited by small samples. Nivolumab plus relatlimab was associated with fewer grade 3-4 TRAEs (23% v 61%) and any-grade TRAEs leading to discontinuation (17% v 41%). CONCLUSION: Nivolumab plus relatlimab demonstrated similar efficacy to nivolumab plus ipilimumab in the overall population, including most-but not all-subgroups, and improved safety in patients with untreated advanced melanoma. Results should be interpreted with caution.
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BACKGROUND: The benefit of intravenous thrombolysis with alteplase before endovascular thrombectomy (EVT) for acute ischemic stroke due to large vessel occlusion remains debated. In this study, we analyzed the cost-effectiveness of EVT alone versus intravenous alteplase before EVT in patients directly admitted to EVT-capable stroke centers from the Dutch health care payer perspective. METHODS: A decision analysis was performed using a Markov model with 15-year simulated follow-up to estimate total costs, quality-adjusted life years, and an incremental cost-effectiveness ratio of intravenous alteplase before EVT compared with EVT alone. A hypothetical cohort of 10â 000 patients with large vessel occlusion aged 70 years was run in Monte Carlo simulation. Functional outcome of each treatment was derived from pooled results of 6 randomized controlled trials (RCTs). Uncertainty was assessed by probabilistic analyses, scenario analyses, and 1-way sensitivity analyses. RESULTS: Using functional outcomes obtained from 6 RCTs (intention-to-treat population), intravenous alteplase before EVT resulted in 0.05 quality-adjusted life years gained at an additional $2817 compared with EVT alone, resulting in the incremental cost-effectiveness ratio of $62â 287. Probabilistic analyses showed that intravenous alteplase before EVT had a probability of 45% and 54%, respectively, of being cost-effective at the $52â 500 and $84â 000 thresholds. Restricting functional outcomes from our post hoc modified as-treated analysis of 6 RCTs (scenario 1), European RCTs (scenario 2), or a Dutch RCT (scenario 3), intravenous alteplase before EVT was cost-effective in 64%, 81%, and 50% of simulations at the $52â 500 threshold, and 79%, 91%, and 67% of simulations at the $84â 000 threshold. CONCLUSIONS: Intravenous alteplase before EVT was not cost-effective in patients with large vessel occlusion in the Netherlands at the $52â 500 threshold but possibly cost-effective at the $84â 000 threshold. Variable functional outcomes at 3 months based on different trial populations affected the cost-effectiveness of intravenous alteplase before EVT.
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Microbially induced nitrogen (N2) gas bubbles can desaturate subsurface areas and thus have been considered as an alternative ground improvement technique for mitigating soil liquefaction potential caused by earthquakes. However, the detailed mechanisms of subsurface N2 bubbles are not well understood and remain a subject of ongoing research. In this study, a transparent microfluidic device was utilized to mimic biological N2 gas bubble formation by nitrate-reducing bacteria and to visually characterize the entire process. During N2 gas formation, a limited number of bubble nucleation sites were identified, which gradually expanded upward through the preferential pore channels. N2 gas bubbles tended to create interconnected gas pockets rather than existing as evenly distributed small gas cavities. The degree of water saturation gradually reduced over a week as the bubbles were produced. The gas ganglia repeatedly grew until they reached the top boundary, which triggered a drastic expulsion of bubbles by ebullition. Despite fluctuations in saturation level, the residual saturation was maintained at around 73 %. Comparative experimental case studies of CO2 gas bubble formation were conducted to identify contrasting gas formation mechanisms. CO2 gas bubbles were generated via the abiotic decompression of a supersaturated CO2 solution under two distinct rates of pressure reduction. Rapid CO2 bubble formation led to uniform nucleation and 41 % residual saturation, while slower formation yielded 35 % due to stable liquid displacement by the gas front. This study highlights the potential of the microfluidic device as an experimental tool for visualizing subsurface gas formation mechanisms. The insights gained could further enhance and optimize geotechnical applications involving gas formation in highly saturated soils.
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MAIN CONCLUSIONS: In contrast to Neltuma species, S. tamarugo exhibited higher stress tolerance, maintaining photosynthetic performance through enhanced gene expression and metabolites. Differentially accumulated metabolites include chlorophyll and carotenoids and accumulation of non-nitrogen osmoprotectants. Plant species have developed different adaptive strategies to live under extreme environmental conditions. Hypothetically, extremophyte species present a unique configuration of physiological functions that prioritize stress-tolerance mechanisms while carefully managing resource allocation for photosynthesis. This could be particularly challenging under a multi-stress environment, where the synthesis of multiple and sequential molecular mechanisms is induced. We explored this hypothesis in three phylogenetically related woody species co-occurring in the Atacama Desert, Strombocarpa tamarugo, Neltuma alba, and Neltuma chilensis, by analyzing their leaf dehydration and freezing tolerance and by characterizing their photosynthetic performance under natural growth conditions. Besides, the transcriptomic profiling, biochemical analyses of leaf pigments, and metabolite analysis by untargeted metabolomics were conducted to study gene expression and metabolomic landscape within this challenging multi-stress environment. S. tamarugo showed a higher photosynthetic capacity and leaf stress tolerance than the other species. In this species, a multifactorial response was observed, which involves high photochemical activity associated with a higher content of chlorophylls and ß-carotene. The oxidative damage of the photosynthetic apparatus is probably attenuated by the synthesis of complex antioxidant molecules in the three species, but S. tamarugo showed the highest antioxidant capacity. Comparative transcriptomic and metabolomic analyses among the species showed the differential expression of genes involved in the biosynthetic pathways of key stress-related metabolites. Moreover, the synthesis of non-nitrogen osmoprotectant molecules, such as ciceritol and mannitol in S. tamarugo, would allow the nitrogen allocation to support its high photosynthetic capacity without compromising leaf dehydration tolerance and freezing stress avoidance.
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Clima Desértico , Fotossíntese , Estresse Fisiológico , Transcriptoma , Fotossíntese/genética , Estresse Fisiológico/genética , Clorofila/metabolismo , Metabolômica , Folhas de Planta/metabolismo , Folhas de Planta/genética , Folhas de Planta/fisiologia , Regulação da Expressão Gênica de Plantas , Perfilação da Expressão Gênica , Carotenoides/metabolismo , Metaboloma/genética , ChileRESUMO
Black dot and silver scurf caused by Colletotrichum coccodes and Helminthosporium solani, respectively, are tuber blemish diseases affecting quality in the fresh and pre-pack potato industry. In the last 20 years, the importance of high-quality tuber appearance has increased considerably due to the growing demand for washed and pre-packed potatoes in the UK. Changing climate characterised by rising temperatures and wetter summers is a threat as this will favour the development of pathogens such as C. coccodes in the soil increasing the risk of food spoilage. Moreover, both diseases can develop not only in the field but also after harvest, with postharvest storage temperatures being a crucial factor in controlling fungal growth. Furthermore, anecdotal evidence showed differences on the aggressiveness of black dot depending on its origin (i.e. England and Scotland) on potato tubers. Silver scurf and black dot are difficult to differentiate as they present similar phenotypes characterised by silvery lesions making it challenging for managers to take the necessary corrective action during storage. Hence, the aim of this study was to give a general insight into the ecological conditions affecting the establishment of the causal agent of potato black dot in the field, and black dot and silver scurf during the supply chain. Therefore, invitro experiments were designed to study the growth rate and lag times simulating both scenarios respectively: on soil extract agar (SEA) media at different temperatures (4, 11, 15 °C) and matric potentials (control [unmodified] and - 1.4 MPa [modified]); and on natural potato dextrose agar (NPDA) for different temperatures (4, 11, 15 and 20 °C) at 99 % relative humidity (RH) for 25 days. When simulating the field environment, drier conditions (matric potential = -1.4 MPa) reduced fungal growth for both isolates by 0.1 cm day-1 at the temperature of 15 °C, suggesting temperature as the main limiting factor for the growth of C. coccodes in the soil. The causal agent of black dot exhibited a faster growth rate under retailer-like conditions (i.e., 15 °C) compared to H. solani. Understanding the environmental influence on both the pathogen and the crop is vital for proper disease management to help reduce food loss and waste.
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Colletotrichum , Tubérculos , Solanum tuberosum , Temperatura , Solanum tuberosum/microbiologia , Colletotrichum/crescimento & desenvolvimento , Colletotrichum/isolamento & purificação , Tubérculos/microbiologia , Tubérculos/crescimento & desenvolvimento , Reino Unido , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Microbiologia de Alimentos , Microbiologia do SoloRESUMO
In this study, the physiological performance and fruit quality responses of the highbush blueberry (Vaccinium corymbosum) cultivar Legacy to high temperatures (HTs) were evaluated in a field experiment. Three-year-old V. corymbosum plants were exposed to two temperature treatments between fruit load set and harvest during the 2022/2023 season: (i) ambient temperature (AT) and (ii) high temperature (HT) (5 °C ± 1 °C above ambient temperature). A chamber covered with transparent polyethylene (100 µm thick) was used to apply the HT treatment. In our study, the diurnal temperature was maintained with a difference of 5.03 °C ± 0.12 °C between the AT and HT treatments. Our findings indicated that HT significantly decreased CO2 assimilation (Pn) by 45% and stomatal conductance (gs) by 35.2% compared to the AT treatment. By contrast, the intercellular CO2 concentration (Ci) showed higher levels (about 6%) in HT plants than in AT plants. Fruit quality analyses revealed that the fruit weight and equatorial diameter decreased by 39% and 13%, respectively, in the HT treatment compared to the AT treatment. By contrast, the firmness and total soluble solids (TSS) were higher in the HT treatment than in the AT treatment. Meanwhile, the titratable acidity showed no changes between temperature treatments. In our study, Pn reduction could be associated with stomatal and non-stomatal limitations under HT treatment. Although these findings improve our understanding of the impact of HTs on fruit growth and quality in V. corymbosum, further biochemical and molecular studies are need.
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OBJECTIVE: To evaluate the postoperative sensitivity (POS), as well as the clinical performance of posterior restorations using a new chemically-cured bulk-fill composite (Stela Automix and Stela Capsule, SDI) comparing with a light-cured bulk-fill composite after 6 months. METHODS: Fifty-five participants with at least three posterior teeth needing restoration were recruited. A total of 165 restorations were performed on Class I or Class II cavities. After the application of Stela primer, the chemically-cured composite (Stela Automix or Stela Capsule) was inserted. For the light-cured composite group, a universal adhesive (Scotchbond Universal) was applied with a bulk-fill composite (Filtek One). Participants were evaluated for spontaneous and stimulated POS in the baseline, after 48 h, 7 days, and 6 months. Additionally, each restoration was assessed using the updated version of FDI criteria after 6 months. The differences in the proportions of the groups were compared by Cochran test statistics (α = 0.05). RESULTS: Both chemically-cured composites showed a lower risk of POS compared to the light-cured composite at baseline and up to 48 h (p < 0.04). A significantly lower surface luster and texture was observed for the Stela Capsule composite compared to the light-cured bulk-fill composite (baseline and 6 months; p = 0.03). A significant color mismatch was observed for the light-cured bulk-fill composite compared to the chemically-cured composites (baseline and 6 months; p = 0.03). No significant differences were observed in any other item evaluations (p > 0.05). CONCLUSION: Chemically-cured composites exhibit lower postoperative sensitivity and less color mismatch compared to a light-cured bulk-fill composite after 6 months of clinical service. CLINICAL SIGNIFICANCE: The chemically-cured composites appear to be an appealing option for restoring posterior teeth, as they exhibit lower postoperative sensitivity compared to a light-cured bulk-fill composite, both at baseline and up to 48 h, and less color mismatch.
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Metabolic dysfunction-associated fatty liver disease (MAFLD) is the liver manifestation of a metabolic syndrome and is highly prevalent in the general population. There has been significant progress in non-invasive tests for MAFLD, from the diagnosis of fatty liver and monitoring of liver fat content in response to intervention, to evaluation of liver fibrosis and its change over time, and from risk stratification of patients within the context of clinical care pathways, to prognostication. Various non-invasive tests have also been developed to assess for fibrotic metabolic dysfunction-associated steatohepatitis, which has emerged as an important diagnostic goal, particularly in the context of clinical trials. Non-invasive tests can be used to diagnose clinically significant portal hypertension so that intervention can be administered to reduce the risk of decompensation. Furthermore, the use of risk stratification algorithms can identify at-risk patients for hepatocellular carcinoma surveillance. Beyond the liver, various tests that evaluate cardiovascular disease risk, assess sarcopenia and measure patient reported outcomes, can be utilized to improve the care of patients with MAFLD. This review provides an up-to-date overview of these non-invasive tests and the limitations of liver biopsy in the management of patients with MAFLD.
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The monosaccharide anhydrides levoglucosan, mannosan, and galactosan are known as 'fire sugars' as they are powerful proxies used to trace fire events. Despite their increasing use, their application is not completely understood, especially in the context of tracing past fire events using sediment samples. There are many uncertainties about fire sugar formation, partitioning, transport, complexation, and stability along all stages of the source-to-sink pathway. While these uncertainties exist, the efficacy of fire sugars as fire tracers remains limited. This study compared high-resolution fire sugar fluxes in freshwater sediment cores to known fire records in Tasmania, Australia. Past fire events correlated with fire sugar flux increases down-core, with the magnitude of the flux inversely proportional to the distance of the fires from the study site. For the first time, fire sugar ratios (levoglucosan/mannosan, L/M) in aerosols were compared with those in sediments from the same time-period. The L/M ratio in surface sediments (1.42-2.58) were significantly lower than in corresponding aerosols (5.08-15.62). We propose two hypotheses that may explain the lower average L/M of sediments. Firstly, the degradation rate of levoglucosan is higher than mannosan in the water column, sediment-water interface, and/or sediment. Secondly, the L/M ratio of non-atmospheric emissions during fires may be lower than that of atmospheric emissions from the same fire. Due to the uncertainties about transport partitioning (atmospheric versus non-atmospheric emissions) and fire sugar degradation along all stages of the source-to-sink pathway, we advise caution when inferring vegetation type (e.g. softwood, hardwood, or grasses) based purely on fire sugar ratios in sediments (e.g. L/M ratio). Future investigations are required to increase the efficacy of fire sugars as a complimentary, or standalone, fire tracer in sediments.
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Worldwide, aquatic biodiversity is severely threatened as a result of anthropogenic pressures such as pollution, habitat destruction and climate change. Widescale legislation resulted in reduced nutrient- and pesticide loads, and restoration measures allowed modest recovery of freshwater biodiversity. However, from 2010 onwards, recovery in the otherwise unrestored aquatic habitats stagnated. The aim of the present study was therefore to reveal long-term trends in aquatic biodiversity in an anthropogenic landscape and to explain the observed patterns. To this end, over 40 years of biomonitoring data of the indicative taxa group Trichoptera (caddisflies), with an exceptionally high spatial and temporal resolution, was employed. Periods of recovery, stagnation, and decline were delineated using linear and non-linear modelling approaches. Subsequently, species were grouped based on abundance patterns over time and this grouping was used to ascertain species-specific responses to anthropogenic stressors using a trait-based approach. Richness and abundance of all Trichoptera jointly, as well as of the five most abundant and the remaining 136 species, significantly increased from 1980 to significant breakpoints from 2010 onwards, after which these metrics, except the abundances of the 5 most abundant, declined significantly. Trend-based species groupings were not significantly explained by biological traits or ecological preferences. However, Trichoptera species increasing in abundance were less sensitive to climate change and poor water quality, or concerned sensitive species which benefited from restoration measures. Species with stable or declining abundances showed higher sensitivity to climate change. The Trichoptera declining in abundance indicated that conditions in non-protected or restored habitats did not improve due to climate change on top of the other anthropogenic pressures. These observations reinforce the need for increased efforts to improve the only moderately restored water- and habitat quality in anthropogenic landscapes to halt further aquatic ecosystem degradation and to turn biodiversity losses again into recoveries.
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Biodiversidade , Mudança Climática , Insetos , Animais , Monitoramento Ambiental , Ecossistema , Especificidade da EspécieRESUMO
BACKGROUND AND AIMS: Improving the care of decompensated cirrhosis is a significant clinical challenge. The primary aim of this trial was to assess the efficacy of a chronic disease management (CDM) model to reduce liver-related emergency admissions (LREA). The secondary aims were to assess model effects on quality-of-care and patient-reported outcomes. APPROACH AND RESULTS: The study design was a 2-year, multicenter, randomized controlled study with 1:1 allocation of a CDM model versus usual care. The study setting involved both tertiary and community care. Participants were randomly allocated following a decompensated cirrhosis admission. The intervention was a multifaceted CDM model coordinated by a liver nurse. A total of 147 participants (intervention=75, control=71) were recruited with a median Model for End-Stage Liver Disease score of 19. For the primary outcome, there was no difference in the overall LREA rate for the intervention group versus the control group (incident rate ratio 0.89; 95% CI: 0.53-1.50, p=0.666) or in actuarial survival (HR=1.14; 95% CI: 0.66-1.96, p=0.646). However, there was a reduced risk of LREA due to encephalopathy in the intervention versus control group (HR=1.87; 95% CI: 1.18-2.96, p=0.007). Significant improvement in quality-of-care measures was seen for the performance of bone density (p<0.001), vitamin D testing (p<0.001), and HCC surveillance adherence (p=0.050). For assessable participants (44/74 intervention, 32/71 controls) significant improvements in patient-reported outcomes at 3 months were seen in self-management ability and quality of life as assessed by visual analog scale (p=0.044). CONCLUSIONS: This CDM intervention did not reduce overall LREA events and may not be effective in decompensated cirrhosis for this end point.
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INTRODUCTION: Women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) have a significantly increased risk of breast cancer, which can be substantially reduced with antiestrogen therapy for chemoprevention. However, antiestrogen therapy for breast cancer risk reduction remains underutilized. Improving knowledge about breast cancer risk and chemoprevention among high-risk patients and their healthcare providers may enhance informed decision-making about this critical breast cancer risk reduction strategy. METHODS/DESIGN: We are conducting a cluster randomized controlled trial to evaluate the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. We have cluster randomized 26 sites across the U.S. through the SWOG Cancer Research Network. A total of 415 patients and 200 healthcare providers are being recruited. They are assigned to standard educational materials alone or combined with the web-based decision support tools. Patient-reported and clinical outcomes are assessed at baseline, after a follow-up visit at 6 months, and yearly for 5 years. The primary outcome is chemoprevention informed choice after the follow-up visit. Secondary endpoints include other patient-reported outcomes, such as chemoprevention knowledge, decision conflict and regret, and self-reported chemoprevention usage. Barriers and facilitators to implementing decision support into clinic workflow are assessed through patient and provider interviews at baseline and mid-implementation. RESULTS/DISCUSSION: With this hybrid effectiveness/implementation study, we seek to evaluate if a multi-level intervention effectively promotes informed decision-making about chemoprevention and provide valuable insights on how the intervention is implemented in U.S. TRIAL REGISTRATION: NCT04496739.
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Neoplasias da Mama , Quimioprevenção , Humanos , Feminino , Neoplasias da Mama/prevenção & controle , Quimioprevenção/métodos , Educação de Pacientes como Assunto/métodos , Técnicas de Apoio para a Decisão , Pessoa de Meia-Idade , Adulto , Tomada de Decisões , Conhecimentos, Atitudes e Prática em Saúde , Comportamento de Redução do Risco , Projetos de Pesquisa , Antagonistas de Estrogênios/uso terapêutico , Antagonistas de Estrogênios/administração & dosagem , Medidas de Resultados Relatados pelo PacienteRESUMO
Identification of taxonomically cryptic species is essential for the effective conservation of biodiversity. Freshwater-limited organisms tend to be genetically isolated by drainage boundaries, and thus may be expected to show substantial cryptic phylogenetic and taxonomic diversity. By comparison, populations of diadromous taxa, that migrate between freshwater and marine environments, are expected to show less genetic differentiation. Here we test for cryptic diversity in Australasian populations (both diadromous and non-diadromous) of two widespread Southern Hemisphere fish species, Galaxias brevipinnis and Galaxias maculatus. Both mtDNA and nuclear markers reveal putative cryptic species within these taxa. The substantial diversity detected within G. brevipinnis may be explained by its strong climbing ability which allows it to form isolated inland populations. In island populations, G. brevipinnis similarly show deeper genetic divergence than those of G. maculatus, which may be explained by the greater abundance of G. maculatus larvae in the sea allowing more ongoing dispersal. Our study highlights that even widespread, 'high-dispersal' species can harbour substantial cryptic diversity and therefore warrant increased taxonomic and conservation attention.
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BACKGROUND AND PURPOSE: Hemorrhagic transformation can occur as a complication of endovascular treatment for acute ischemic stroke. This study aimed to determine whether ischemia depth as measured by admission CTP metrics can predict the development of hemorrhagic transformation at 24 hours. MATERIALS AND METHODS: Patients with baseline CTP and 24-hour follow-up imaging from the ESCAPE-NA1 trial were included. RAPID software was used to generate CTP volume maps for relative CBF, CBV, and time-to-maximum at different thresholds. Hemorrhage on 24-hour imaging was classified according to the Heidelberg system, and volumes were calculated. Univariable and multivariable regression analyses assessed the association between CTP lesion volumes and hemorrhage/hemorrhage subtypes. RESULTS: Among 408 patients with baseline CTP, 142 (35%) had hemorrhagic transformation at 24-hour follow-up, with 89 (63%) classified as hemorrhagic infarction (HI1/HI2), and 53 (37%), as parenchymal hematoma (PH1/PH2). Patients with HI or PH had larger volumes of low relative CBF and CBV at each threshold compared with those without hemorrhage. After we adjustied for baseline and treatment variables, only increased relative CBF <30% lesion volume was associated with any hemorrhage (adjusted OR, 1.14; 95% CI, 1.02-1.27 per 10 mL), as well as parenchymal hematoma (adjusted OR, 1.23; 95% CI, 1.06-1.43 per 10 mL). No significant associations were observed for hemorrhagic infarction. CONCLUSIONS: Larger "core" volumes of relative CBF <30% were associated with an increased risk of PH following endovascular treatment. This particular metric, in conjunction with other clinical and imaging variables, may, therefore, help estimate the risk of post-endovascular treatment hemorrhagic complications.
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Procedimentos Endovasculares , AVC Isquêmico , Humanos , Masculino , Feminino , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/cirurgia , Idoso , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Pessoa de Meia-Idade , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Tomografia Computadorizada por Raios X , Idoso de 80 Anos ou maisRESUMO
The accumulation of crystal calcium oxalate (CaOx) in plants is linked to a type of stress-induced photosynthesis termed 'alarm photosynthesis', serving as a carbon reservoir when carbon dioxide (CO2) exchange is constrained. Colobanthus quitensis is an extremophyte found from southern Mexico to Antarctica, which thrives in high-altitude Andean regions. Growing under common garden conditions, C. quitensis from different latitudinal provenances display significant variations in CaOx crystal accumulation. This raises the following questions: are these differences maintained under natural conditions? And is the CaOx accumulation related to mesophyll conductance (gm) and net photosynthesis (AN) performed in situ? It is hypothesized that in provenances with lower gm, C. quitensis will exhibit an increase in the use of CaOx crystals, resulting in reduced crystal leaf abundance. Plants from Central Chile (33°), Patagonia (51°), and Antarctica (62°) were measured in situ and sampled to determine gas exchange and CaOx crystal accumulation, respectively. Both AN and gm decrease towards higher latitudes, correlating with increases in leaf mass area and leaf density. The crystal accumulation decreases at higher latitudes, correlating positively with AN and gm. Thus, in provenances where environmental conditions induce more xeric traits, the CO2 availability for photosynthesis decreases, making the activation of alarm photosynthesis feasible as an internal source of CO2.
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Deep brain stimulation (DBS) of the subthalamic nucleus (STN) produces an electrophysiological signature called evoked resonant neural activity (ERNA); a high-frequency oscillation that has been linked to treatment efficacy. However, the single-neuron and synaptic bases of ERNA are unsubstantiated. This study proposes that ERNA is a subcortical neuronal circuit signature of DBS-mediated engagement of the basal ganglia indirect pathway network. In people with Parkinson's disease, we: (i) showed that each peak of the ERNA waveform is associated with temporally-locked neuronal inhibition in the STN; (ii) characterized the temporal dynamics of ERNA; (iii) identified a putative mesocircuit architecture, embedded with empirically-derived synaptic dynamics, that is necessary for the emergence of ERNA in silico; (iv) localized ERNA to the dorsal STN in electrophysiological and normative anatomical space; (v) used patient-wise hotspot locations to assess spatial relevance of ERNA with respect to DBS outcome; and (vi) characterized the local fiber activation profile associated with the derived group-level ERNA hotspot.
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Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Doença de Parkinson/terapia , Estimulação Encefálica Profunda/métodos , Núcleo Subtalâmico/fisiologia , Gânglios da Base/fisiologia , Neurônios/fisiologiaRESUMO
BACKGROUND: Endovascular treatment (EVT) has become standard of care for patients with anterior circulation large vessel occlusion (LVO) stroke, with indications having recently expanded to late time-window and large ischemic core patients. There is conflicting evidence on whether EVT reduces mortality or only disability. We performed a meta-analysis of randomized controlled trials (RCTs) to assess the effect of EVT on mortality and severe disability. METHODS: We systematically searched PubMed, Web of Science, Scopus, and Embase on November 15, 2023, to identify phase 3 RCTs comparing EVT to best medical treatment (BMT) in patients with anterior circulation LVO stroke in a common effects meta-analysis. The primary outcome was mortality at 3 months. Secondary outcomes were moderately severe or severe disability (modified Rankin Scale (mRS) score 4-5) at 3 months. RESULTS: 18 studies comparing EVT to BMT were included, with a total of 4309 patients; 2159 that were treated with EVT, and 2150 treated with BMT. Mortality was significantly lower in the EVT group than in the BMT group (odds ratio (OR): 0.81, 95% CI: 0.70-0.94). Proportions of moderately severe or severe disability (OR: 0.55, 95% CI: 0.48-0.62) were also significantly lower in patients treated with EVT. CONCLUSIONS: This meta-analysis suggests that EVT reduces both mortality and moderately severe or severe disability in patients with anterior circulation LVO stroke.
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Procedimentos Endovasculares , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Procedimentos Endovasculares/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/terapia , Pessoas com Deficiência , Avaliação da DeficiênciaAssuntos
Colina , Hiperparatireoidismo Secundário , Compostos Radiofarmacêuticos , Humanos , Colina/análogos & derivados , Hiperparatireoidismo Secundário/diagnóstico por imagem , Hiperparatireoidismo Secundário/sangue , Radioisótopos de Flúor , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Hiperparatireoidismo/diagnóstico por imagem , Hiperparatireoidismo/sangueRESUMO
BACKGROUND: Cardiac computed tomography (CT) acquired during the initial acute stroke imaging protocol (acute cardiac CT) is increasingly used to screen for cardioembolism, but information on the long-term clinical implications of its findings is lacking. METHODS AND RESULTS: We performed a prospective, single-center cohort study in which consecutive patients with ischemic stroke underwent ECG-gated acute cardiac CT and were followed up for 2 years. The primary outcome was functional outcome assessed using the modified Rankin Scale. Secondary outcomes were death and occurrence of major adverse cardiovascular events (composite of recurrent ischemic stroke, myocardial infarction, and cardiovascular death). We compared patients with and without a high-risk structural source of embolism on acute cardiac CT. Of 452 included patients, 55 (12.2%) had a high-risk source of embolism, predominantly cardiac thrombi (38 patients) and signs of endocarditis (8 patients). Follow-up at 2 years was complete for 430 (95.1%) patients. Patients with a high-risk source of embolism had a worse functional outcome (median modified Rankin Scale, 6 [IQR, 2-6] versus 2 [IQR, 1-5]; adjusted common odds ratio, 2.92 [95% CI, 1.62-5.25]), increased mortality rate (52.7% versus 23.7%; adjusted hazard ratio [HR], 3.28 [95% CI, 1.94-5.52]), and major adverse cardiovascular events (38.9% versus 17.5%; adjusted HR, 3.20 [95% CI, 1.80-5.69]). A high-risk source of embolism was not associated with recurrent ischemic stroke (11.1% versus 9.6%; adjusted HR, 1.30 [95% CI, 0.49-3.44]). CONCLUSIONS: Structural high-risk sources of embolism on acute cardiac CT in patients with ischemic stroke were associated with poor long-term functional outcome and occurrence of major adverse cardiovascular events but not with recurrent stroke.