Challenges to the operation of Brazilian LTCIs and changes in oversight.

BACKGROUND: Despite 18 years since health surveillance regulations were promulgated in Brazil to govern Long-Term Care Institutions for Older Adults (LTCIs), many institutions fail to comply with the Differentiated Regime for Public Procurement (Resolution No. 502/2021) due to structural and operational conditions. This study aimed to investigate Brazilian LTCI managers' understanding of challenges that significantly impact institutional operation and gather suggestions for enhancing RDC No. 502/21. METHODS: A cross-sectional, exploratory, and qualitative study was conducted, involving 90 managers or technical supervisors from Brazilian LTCIs. Data were collected using a self-administered Google Forms instrument and analyzed through Thematic Analysis based on the Organizing for Quality (OQ) framework. RESULTS: The most impactful challenges for LTCIs were healthcare, financing, human resources, relationship with oversight bodies, and family members. DISCUSSION: Proposed improvements for RDC No. 502/21 included enhanced professional training, infrastructure revision, increased financial support from the state, realistic oversight/regulations, and tailored monitoring approaches. CONCLUSION: LTCIs in Brazil face numerous challenges, and the suggested improvements aim to adapt regulations to institutional realities. However, considering the regulations' variability and purposes, further investigation is warranted.

Vacuum-assisted excision: a safe minimally invasive option for benign phyllodes tumor diagnosis and treatment-a systematic review and meta-analysis.

Synopsis: This is a systematic review and meta-analysis comparing surgical excision with percutaneous ultrasound-guided vacuum-assisted excision (US-VAE) for the treatment of benign phyllodes tumor (PT) using local recurrence (LR) as the endpoint. Objective: To determine the frequency of local recurrence (LR) of benign phyllodes tumor (PT) after ultrasound-guided vacuum-assisted excision (US-VAE) compared to the frequency of LR after surgical excision. Method: A systematic review and meta-analysis [following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard] was conducted by comparing LR in women older than 18 years treated for benign PT by US-VAE compared with local surgical excision with at least 12 months of follow-up. Studies were retrieved from PubMed, Scopus, Web of Science, and Embase. The pooled effect measure used was the odds ratio (OR) of recurrence. Results: Five comparative prospective or retrospective observational studies published between January 1, 1992, and January 10, 2022, comparing surgical excision with percutaneous US-VAE for LR of benign PT met the selection criteria. Four were retrospective observational cohorts, and one was a prospective observational cohort. A total of 778 women were followed up. Of them, 439 (56.4%) underwent local surgical excision, and 339 (43.6%) patients had US-VAE. The median age of patients in the five studies ranged from 33.7 to 39 years; the median size ranged from 1.5 cm to 3.0 cm, and the median follow-up ranged from 12 months to 46.6 months. The needle gauge ranged from 7G to 11G. LR rates were not statically significant between US-VAE and surgical excision (41 of 339 versus 34 of 439; OR 1.3; p = 0.29). Conclusion: This meta-analysis suggests that using US-VAE for the removal of benign PT does not increase local regional recurrence and is a safe minimally invasive therapeutic option. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022309782.

Posterior circulation collaterals as predictors of outcome in basilar artery occlusion: a sub-analysis of the BASICS randomized trial.

Introduction and purpose: Basilar artery occlusion (BAO) is still one of the most devastating neurological conditions associated with high morbidity and mortality. In the present study, we aimed to assess the role of posterior circulation collaterals as predictors of outcome in the BASICS trial and to compare two grading systems (BATMAN score and PC-CS) in terms of prognostic value. Methods: We performed a sub-analysis of the BASICS trial. Baseline clinical and imaging variables were analyzed. For the imaging analysis, baseline CT and CTA were analyzed by a central core lab. Only those patients with good or moderate quality of baseline CTA and with confirmed BAO were included. Multivariable binary logistic regression analysis was used to test the independent association of clinical and imaging characteristics with a favorable outcome at 3 months (defined as a modified Rankin Score of ≤3). ROC curve analysis was used to assess and compare accuracy between the two collateral grading systems. Results: The mean age was 67.0 (±12.5) years, 196 (65.3%) patients were males and the median NIHSS was 21.5 (IQR 11-35). Median NCCT pc-ASPECTS was 10 (IQR10-10) and median collateral scores for BATMAN and PC-CS were 8 (IQR 7-9) and 7 (IQR 6-8) respectively. Collateral scores were associated with favorable outcome at 3 months for both BATMAN and PC-CS but only with a modest accuracy on ROC curve analysis (AUC 0.62, 95% CI [0.55-0.69] and 0.67, 95% CI [0.60-0.74] respectively). Age (OR 0.97, 95% CI [0.95-1.00]), NIHSS (OR 0.91, 95% CI [0.89-0.94]) and collateral score (PC-CS - OR 1.2495% CI [1.02-1.51]) were independently associated with clinical outcome. Conclusion: The two collateral grading systems presented modest prognostic accuracy. Only the PC-CS was independently associated with a favorable outcome at 3 months.

An integrated view of cisplatin-induced nephrotoxicity, hepatotoxicity, and cardiotoxicity: characteristics, common molecular mechanisms, and current clinical management.

Cisplatin (CP) is a chemotherapy drug widely prescribed to treat various neoplasms. Although fundamental for the therapeutic action of the drug, its cytotoxic mechanisms trigger adverse effects in several tissues, such as the kidney, liver, and heart, which limit its clinical use. In this sense, studies point to an essential role of damage to nuclear and mitochondrial DNA associated with oxidative stress, inflammation, and apoptosis in the pathophysiology of tissue injuries. Due to the limitation of effective preventive and therapeutic measures against CP-induced toxicity, new strategies with potential cytoprotective effects have been studied. Therefore, this article is timely in reviewing the characteristics and main molecular mechanisms common to renal, hepatic, and cardiac toxicity previously described, in addition to addressing the main validated strategies for the current management of these adverse events in clinical practice. We also handle the main promising antioxidant substances recently presented in the literature to encourage the development of new research that consolidates their potential preventive and therapeutic effects against CP-induced cytotoxicity.

Imaging associations enhance the understanding of ECG abnormalities in male Brazilian football players: findings from the B-Pro Foot ECG study.

OBJECTIVES: To evaluate the prevalence of abnormal ECG findings and their association with imaging results in male Brazilian football players. METHODS: The 'B-Pro Foot ECG' is a multicentre observational study conducted in 82 Brazilian professional clubs. It analysed 6125 players aged 15-35 years (2496 white, 2004 mixed-race and 1625 black individuals) who underwent cardiovascular screening from 2002 to 2023. All ECGs were reviewed by two experienced cardiologists in the athlete's care. Those with abnormal findings underwent further investigations, including a transthoracic echocardiogram (TTE). Cardiac magnetic resonance (CMR) was subsequently performed based on TTE findings or clinical suspicion. RESULTS: In total, 180 (3%) players had abnormal ECGs and 176 (98%) showed normal TTE results. Athletes aged 26-35 years had a higher prevalence of abnormal ECGs than younger athletes (15-25 years). Black players had a higher prevalence of T-wave inversion (TWI) in the inferior leads than white players (2.6% vs 1.4%; p=0.005), as well as in V5 (2.9%) and V6 (2.1%) compared with white (1.2% and 1.0%; p<0.001) and mixed-race (1.5% and 1.2%; p<0.05) players, respectively. TTE parameters were similar across ethnicities. However, four out of 75 players with inferolateral TWI showed abnormal TTEs and CMR findings consistent with cardiomyopathies. CMR also showed cardiomyopathies or myocarditis in four players with inferolateral TWI and normal TTEs. In total, nine (0.1%) athletes were diagnosed with cardiac diseases and were followed for 40±30 months, with no cardiac events documented. CONCLUSION: This study found a 3% prevalence of abnormal ECGs in male Brazilian football players. Inferolateral TWI was associated with cardiac pathologies confirmed by CMR, even in athletes with a normal TTE.

RapidpulseTM cyclic aspiration system for acute ischemic stroke due to large vessel occlusions.

BACKGROUND: The best strategy to achieve optimal reperfusion outcomes during mechanical thrombectomy remains to be defined. The RapidPulseTM Cyclic Aspiration System is a novel technology, delivering high-frequency pulsed vacuum forces to increase the efficiency of aspiration thrombectomy. METHODS: Prospective, multicenter, open-label, core lab-adjudicated, two-arm study comparing safety and efficacy of a feasibility version of the RapidPulseTM system compared with contemporary controls. Primary endpoint was the rate of mTICI ≥ 2c after first-pass effect (FPE). Additional efficacy endpoints were the rates of mTICI ≥ 2b after first pass (modified FPE (mFPE)), last pass with study device defined as frontline technical success, and after all passes including rescue therapy. The primary safety endpoints included symptomatic ICH (sICH) within 24 h post-procedure. RESULTS: Between February 2022 to December 2022, 80 subjects were consented and enrolled in the study (n = 40 treatment arm, n = 40 control arm). In the intent to treat (ITT) population, mean age was 67.8 ± 11.5 years; 19 (47.5%) were male. Median NIHSS score was 16 (IQR: 13-22). Median ASPECTS score was 9 (IQR: 8-10). The rate of mTICI ≥ 2c after first pass was 53.9% in ITT population (60.0% in per-protocol population) versus 38.5% in the corresponding control population. Functional independence (mRS 0-2) at 90 days was achieved in 61.1% (22/36) in the RapidPulseTM arm and 52.8% (19/36) in the control arm. In the RapidPulseTM arm, no sICH within 24 h and no device-related morbidity or mortality occurred. CONCLUSION: Preliminary data suggests RapidPulseTM Aspiration System is highly effective and safe for recanalization of large vessel occlusions.

Petrosamine isolated from marine sponge Petrosia sp. demonstrates protection against neurotoxicity in vitro and in vivo.

According to The World Alzheimer Report 2023 by Alzheimer's Disease International (ADI) estimates that 33 to 38.5 million people worldwide suffer from Alzheimer's Disease (AD). A crucial hallmark associated with this disease is associated with the deficiency of the brain neurotransmitter acetylcholine, due to an affected acetylcholinesterase (AChE) activity. Marine organisms synthesize several classes of compounds, some of which exhibit significant AChE inhibition, such as petrosamine, a coloured pyridoacridine alkaloid. The aim of this work was to characterize the activity of petrosamine isolated for the first time from a Brazilian marine sponge, using two neurotoxicity models with aluminium chloride, as exposure to aluminium is associated with the development of neurodegenerative diseases. The in vitro model was based in a neuroblastoma cell line and the in vivo model exploited the potential of zebrafish (Danio rerio) embryos in mimicking hallmarks of AD. To our knowledge, this is the first report on petrosamine's activity over these parameters, either in vitro or in vivo, in order to characterize its full potential for tackling neurotoxicity.

Location versus ID: what matters to lung-resident memory T cells?

Tissue-resident memory T cells (TRM cells) are vital for the promotion of barrier immunity. The lung, a tissue constantly exposed to foreign pathogenic or non-pathogenic antigens, is not devoid of these cells. Lung TRM cells have been considered major players in either the protection against respiratory viral infections or the pathogenesis of lung allergies. Establishment of lung TRM cells rely on intrinsic and extrinsic factors. Among the extrinsic regulators of lung TRM cells, the magnitude of the impact of factors such as the route of antigen entry or the antigen natural tropism for the lung is not entirely clear. In this perspective, we provide a summary of the literature covering this subject and present some preliminary results on this potential dichotomy between antigen location versus antigen type. Finally, we propose a hypothesis to synthesize the potential contributions of these two variables for lung TRM cell development.

A simplified BRADEN scale for the risk of developing pressure injuries.

BACKGROUND: Pressure injuries (PIs) are a major problem for healthcare providers, impacting both care costs and patients' quality of life, although they are predominately preventable. These injuries are especially present in Intensive Care Units (ICUs) as a result of the severity of the clinical conditions of patients in this unit. AIM: To develop a simplified version of the Braden scale by removing two of the most subjective subscores-Nutrition and Sensory Perception-in an attempt to reduce the chance of errors by the nursing team during the application of the scale. STUDY DESIGN: A cross-sectional study was conducted on data collected from patients admitted to the ICU of a private Brazilian tertiary hospital. The resulting data consisted of 5194 patients, 6353 hospital admissions, and 6974 ICU stays. The overall prevalence of PI was 1.09%. RESULTS: The T-test showed that both the Braden and the simplified Braden scores were significantly different between patients with and without PI (p < .001). Patients who developed PIs scored lower than those who did not. The area under the Receiver Operating Characteristic curve of the Braden Scale was 74.21% (95% CI: 68.61%-79.8%) and of the simplified scale was 72.54% (95% CI: 66.87%-78.22%). The Positive Predictive Value of the Braden Scale was 3.17% when interpolated at the same sensitivity as the simplified scale (47.37%), which achieved 3.26%. CONCLUSIONS: By removing two of the six subscores of the Braden scale we propose a new tool for identifying patients at risk of developing PI in a more objective and fast way. Our results show that classification performance had little negative impact. RELEVANCE TO CLINICAL PRACTICE: A simplified, less subjective scale allows for more precise and less time-consuming risk classification.

CD8+ T Cells Keep Their (K+)urrency for Function.

CD8+ T-cell responses are influenced by ion abundance, which can widely vary within the tumor microenvironment. In this issue, Collier and colleagues investigated how intracellular versus extracellular potassium ion (K+) regulates intratumoral CD8+ T cells. They show that, while excessive extracellular K+ induces exhaustion, intracellular K+ is needed for protection from dysfunction. This work shows additional evidence that the regulation of CD8+ T-cell responses depends on a fine balance between intracellular and extracellular metabolite levels. See related article by Collier et al., p. 36 (2) .

3-min All-out Test to Evaluate Aerobic and Anaerobic Indexes in Court Team Sports.

This study aimed to test the reproducibility of the 3-min all-out effort applied using shuttle running and compare its values to aerobic parameters. On the first day, 14 futsal players underwent an exhaustive test to determine the maximal incremental speed (MIS) and anaerobic threshold (AnT). On the second day, the participants performed the 3-min all-out effort (n=14), which was repeated after 48 h (third day) to test its reproducibility (n=11). Peak oxygen consumption (V̇ O2PEAK) and peak blood lactate concentrations ([La-]) were determined from 3-min all-out efforts performed through a 20-m shuttle run on the official court. The distance covered, mean speed, and critical speed (CS) during the 3-min all-out presented direct relationships with aerobic parameters determined through the incremental test (r>0.62). The distance covered above CS (D') presented a direct relationship with peak lactate concentrations induced by a 3-min all-out effort (r=0.81). Despite the acceptable levels of reproducibility observed for most of the 3-min all-out variables, the minimal detectable change for D' was high (72%). Our results demonstrated the potential use of mean speed to evaluate aerobic fitness. However, the applicability of the 3-min all-out shuttle run test to monitor training adaptations should be avoided, at least in nonexperienced athletes.

Relação entre saúde mental de idosos do Distrito Federal e exposição a informações sobre COVID-19

A fim de conhecer o tempo e a frequência com que idosos se expõem a notícias e informações sobre a COVID-19 por diferentes mídias e relacioná-los com sintomas depressivos e de ansiedade, 154 idosos (M = 69,06) do Distrito Federal responderam a um questionário online. A amostra foi composta majoritariamente por mulheres, brancas, escolarizadas e com renda proveniente de aposentadoria e/ou pensão. Constatou-se que a televisão foi o meio de comunicação mais utilizado pelos participantes, seguido pelas redes sociais. Ao considerar características demográficas, idosos mais jovens (60 a 74 anos) e com ensino superior completo apresentaram maior exposição a notícias por meio das redes sociais do que os mais velhos e com menor escolaridade. Idosos com rastreio para depressão e transtorno de ansiedade generalizada permaneceram mais horas expostos a informações sobre a COVID-19 veiculadas pela televisão que idosos não rastreados. Além disso, aqueles com rastreio para depressão relataram maior frequência de exposição a esse conteúdo pela televisão e pelas redes sociais. Os resultados deste estudo revelam a necessidade de planejamento de medidas de promoção e prevenção em saúde específicas para a população idosa a fim de lidar com as consequências da pandemia e, especialmente, infodemia de COVID-19.

Para conocer el tiempo y la frecuencia con que los ancianos están expuestos a noticias e informaciones sobre el COVID-19 por diferentes medios de comunicación y relacionarlos con los síntomas depresivos y de ansiedad, 154 ancianos (m = 69,06) del Distrito Federal respondieron a un cuestionario online. La muestra estaba compuesta mayoritariamente por mujeres, de raza blanca, con estudios y con ingresos por jubilación y/o pensión. Se comprobó que la televisión era el medio de comunicación más utilizado por los participantes, seguido de las redes sociales. Teniendo en cuenta las características demográficas, los más jóvenes (60 a 74 años) y con estudios superiores completos presentan una mayor exposición a las noticias a través de las redes sociales que los más mayores y con menor escolaridad. Los ancianos con cribado de depresión y trastorno de ansiedad generalizada permanecieron más horas expuestos a la información sobre COVID-19 emitida por televisión que los ancianos no cribados. Además, los que se sometieron a pruebas de detección de la depresión informaron de una mayor frecuencia de exposición a este contenido por parte de la televisión y los medios sociales. Los resultados de este estudio revelan la necesidad de planificar medidas de promoción de la salud y de prevención específicas para la población de edad avanzada con el fin de hacer frente a las consecuencias de la pandemia y, especialmente, de la infodemia de COVID-19.

In order to know the time and frequency with which elderly are exposed to news and information about COVID-19 through different media and relate them with depressive and anxiety symptoms, 154 elderly (M = 69.06) from Distrito Federal answered an online questionnaire. The sample was composed mostly of women, white, educated, and with income from retirement and/or pension. It was found that television was the media most used by participants, followed by social networks. Considering demographic characteristics, younger elders (60 to 74 years old) and with complete college education had more exposure to news through social networks than the older ones and with less education. Elderly with screening for depression and generalized anxiety disorder remained exposed more hours to information about COVID-19 broadcast on television than unscreened elderly. In addition, those with screening for depression reported greater frequency of exposure to this content on television and social media. The results of this study reveal the need for health promotion and prevention measures planning specific to the elderly population to deal with the consequences of the pandemic and especially infodemic of COVID-19.

Mercury cyanide complexes and their relevance as environmental contaminants.

This review addresses the formation and relevance of mercury cyanide complexes as environmental contaminants. Gold extraction is traditionally carried out through the process of mercury amalgamation (Hg) due to its simplicity and low cost. However, this process is inefficient, capturing only about 30% of the gold present in the processed material. Additionally, mercury is toxic, mobile, and capable of accumulating in aquatic ecosystems, leading to its prohibition in several countries. As an alternative, cyanidation has been widely used in gold extraction. However, the frequent combination of Hg amalgamation with cyanidation can result in the formation of mercury cyanide complexes, which can be released into local water bodies, potentially impacting human health and the environment. This article reviews the existing knowledge of these complexes and highlights the remaining gaps in understanding their environmental behavior. It also emphasizes the need to address concerns related to the formation of these complexes and seek solutions to minimize their negative impacts. Furthermore, the article highlights the lack of updates in the literature regarding the impacts of cyanidation and the limited availability of comprehensive information on the topic. It is essential to conduct updated research in this area to advance knowledge and promote safer and more responsible practices in the mining industry.

The presence of depressive symptoms and cognitive performance among older individuals with and without self-reported chronic diseases.

Dementias secondary to cardiovascular diseases are the second cause of neurogenerative diseases. These conditions can be prevented by controlling risk factors, and it is necessary to observe the relationship between chronic diseases. Objective: to know the influence of chronic non-communicable diseases on cognition and depressive symptoms in the elderly, amid the COVID-19 pandemic. Methods: 578 older adults were evaluated using a sociodemographic questionnaire, the Brazilian Telephone version of the Mini Mental State Examination (Braztel-MMSE), the Geriatric Depression Scale (GDS-15) and an open questionnaire related to NCDs. Results: the association of Non-Communicable Diseases (NCD) with age, depressive symptoms and schooling was confirmed. Conclusion: no association with cognitive decline was evident due to the relationship of high schooling of participants and control of NCDs.

As demências secundárias às doenças cardiovasculares são a segunda causa de doenças neurodegenerativas. Essas condições podem ser prevenidas pelo controle de fatores de risco, sendo necessário observar a relação entre doenças crônicas. Objetivo: Conhecer a influência das doenças crônicas não transmissíveis (DCNT) na cognição e nos sintomas depressivos em pessoas idosas, em meio à pandemia da COVID-19. Métodos: Foram avaliados 578 idosos utilizando um questionário sociodemográfico, o Brazilian telephone version of the Mini Mental State Examination (Braztel-MMSE), a Escala de Depressão Geriátrica (GDS-15) e um questionário aberto relacionado às DCNT. Resultados: Foi confirmada a associação das DCNT crônicas com idade, sintomas depressivos e escolaridade. Conclusão: Nenhuma associação com declínio cognitivo foi evidente em razão da relação da alta escolaridade dos participantes com o controle das DCNT.

Performance of RAPID noncontrast CT stroke platform in large vessel occlusion and intracranial hemorrhage detection.

Background: Noncontrast CT (NCCT) is used to evaluate for intracerebral hemorrhage (ICH) and ischemia in acute ischemic stroke (AIS). Large vessel occlusions (LVOs) are a major cause of AIS, but challenging to detect on NCCT. Aims: The purpose of this study is to evaluate an AI software called RAPID NCCT Stroke (RAPID, iSchemaView, Menlo Park, CA) for ICH and LVO detection compared to expert readers. Methods: In this IRB approved retrospective, multicenter study, stand-alone performance of the software was assessed based on the consensus of 3 neuroradiologists and sensitivity and specificity were determined. The platform's performance was then compared to interpretation by readers comprised of eight general radiologists (GR) and three neuroradiologists (NR) in detecting ICH and hyperdense vessel sign (HVS) indicating LVO. Results: A total of 244 cases were included. Of the 244, 115 were LVOs and 26 were ICHs. One hundred three cases did not have LVO nor ICH. Stand-alone performance of the software demonstrated sensitivities and specificities of 96.2 and 99.5% for ICH and 63.5 and 95.1% for LVO detection. Compared to all 11 readers and eight GR readers only respectively, the software demonstrated superiority, achieving significantly higher sensitivities (63.5% versus 43.6%, p < 0.0001 and 63.5% versus 40.9%, p = 0.001). Conclusion: The RAPID NCCT Stroke platform demonstrates superior performance to radiologists for detecting LVO from a NCCT. Use of this software platform could lead to earlier LVO detection and expedited transfer of these patients to a thrombectomy capable center.

T cell-specific P2RX7 favors lung parenchymal CD4+ T cell accumulation in response to severe lung infections.

CD4+ T cells are key components of the immune response during lung infections and can mediate protection against tuberculosis (TB) or influenza. However, CD4+ T cells can also promote lung pathology during these infections, making it unclear how these cells control such discrepant effects. Using mouse models of hypervirulent TB and influenza, we observe that exaggerated accumulation of parenchymal CD4+ T cells promotes lung damage. Low numbers of lung CD4+ T cells, in contrast, are sufficient to protect against hypervirulent TB. In both situations, lung CD4+ T cell accumulation is mediated by CD4+ T cell-specific expression of the extracellular ATP (eATP) receptor P2RX7. P2RX7 upregulation in lung CD4+ T cells promotes expression of the chemokine receptor CXCR3, favoring parenchymal CD4+ T cell accumulation. Our findings suggest that direct sensing of lung eATP by CD4+ T cells is critical to induce tissue CD4+ T cell accumulation and pathology during lung infections.

Lyotropic liquid crystalline 2D and 3D mesophases: Advanced materials for multifunctional anticancer nanosystems.

Cancer remains a leading cause of mortality. Despite significant breakthroughs in conventional therapies, treatment is still far from ideal due to high toxicity in normal tissues and therapeutic inefficiency caused by short drug lifetime in the body and resistance mechanisms. Current research moves towards the development of multifunctional nanosystems for delivery of chemotherapeutic drugs, bioactives and/or radionuclides that can be combined with other therapeutic modalities, like gene therapy, or imaging to use in therapeutic screening and diagnosis. The preparation and characterization of Lyotropic Liquid Crystalline (LLC) mesophases self-assembled as 2D and 3D structures are addressed, with an emphasis on the unique properties of these nanoassemblies. A comprehensive review of LLC nanoassemblies is also presented, highlighting the most recent advances and their outstanding advantages as drug delivery systems, including tailoring strategies that can be used to overcome cancer challenges. Therapeutic agents loaded in LLC nanoassemblies offer qualitative and quantitative enhancements that are superior to conventional chemotherapy, particularly in terms of preferential accumulation at tumor sites and promoting enhanced cancer cell uptake, lowering tumor volume and weight, improving survival rates, and increasing the cytotoxicity of their loaded therapeutic agents. In terms of quantitative anticancer efficacy, loaded LLC nanoassemblies reduced the IC50 values from 1.4-fold against lung cancer cells to 125-fold against ovarian cancer cells.

Adenosine A2A receptors control generalization of contextual fear in rats.

Fear learning is essential to survival, but traumatic events may lead to abnormal fear consolidation and overgeneralization, triggering fear responses in safe environments, as occurs in post-traumatic stress disorder (PTSD). Adenosine A2A receptors (A2AR) control emotional memory and fear conditioning, but it is not known if they affect the consolidation and generalization of fear, which was now investigated. We now report that A2AR blockade through systemic administration of the A2AR antagonist SCH58261 immediately after contextual fear conditioning (within the consolidation window), accelerated fear generalization. Conversely, A2AR activation with CGS21680 decreased fear generalization. Ex vivo electrophysiological recordings of field excitatory post-synaptic potentials (fEPSPs) in CA3-CA1 synapses and of population spikes in the lateral amygdala (LA), showed that the effect of SCH58261 is associated with a reversion of fear conditioning-induced decrease of long-term potentiation (LTP) in the dorsal hippocampus (DH) and with increased amplitude of LA LTP in conditioned animals. These data suggest that A2AR are engaged during contextual fear consolidation, controlling long-term potentiation mechanisms in both DH and LA during fear consolidation, impacting on fear generalization; this supports targeting A2AR during fear consolidation to control aberrant fear processing in PTSD and other fear-related disorders.

Factors Affecting Enteric Emission Methane and Predictive Models for Dairy Cows.

Enteric methane emission is the main source of greenhouse gas contribution from dairy cattle. Therefore, it is essential to evaluate drivers and develop more accurate predictive models for such emissions. In this study, we built a large and intercontinental experimental dataset to: (1) explain the effect of enteric methane emission yield (g methane/kg diet intake) and feed conversion (kg diet intake/kg milk yield) on enteric methane emission intensity (g methane/kg milk yield); (2) develop six models for predicting enteric methane emissions (g/cow/day) using animal, diet, and dry matter intake as inputs; and to (3) compare these 6 models with 43 models from the literature. Feed conversion contributed more to enteric methane emission (EME) intensity than EME yield. Increasing the milk yield reduced EME intensity, due more to feed conversion enhancement rather than EME yield. Our models predicted methane emissions better than most external models, with the exception of only two other models which had similar adequacy. Improved productivity of dairy cows reduces emission intensity by enhancing feed conversion. Improvement in feed conversion should be prioritized for reducing methane emissions in dairy cattle systems.