A novel alpha-synuclein G14R missense variant is associated with atypical neuropathological features.

Background: Parkinson's disease (PD) affects millions of people worldwide, but only 5-10% of patients suffer from a monogenic form of the disease with Mendelian inheritance. SNCA, the gene encoding for the protein alpha-synuclein (aSyn), was the first to be associated with familial forms of PD and, since then, several missense variants and multiplications of the SNCA gene have been established as rare causes of autosomal dominant forms of PD. Aim and methods: A patient carrying aSyn missense mutation and his family members were studied. We present the clinical features, genetic testing - whole exome sequencing (WES), and neuropathological findings. The functional consequences of this aSyn variant were extensively investigated using biochemical, biophysical, and cellular assays. Results: The patient exhibited a complex neurodegenerative disease that included generalized myocloni, bradykinesia, dystonia of the left arm and apraxia. WES identified a novel heterozygous SNCA variant (cDNA 40G>A; protein G14R). Neuropathological examination showed extensive atypical aSyn pathology with frontotemporal lobar degeneration (FTLD) and nigral degeneration pattern with abundant ring-like neuronal inclusions, and few oligodendroglial inclusions. Sanger sequencing confirmed the SNCA variant in the healthy, elderly parent of the patient suggesting incomplete penetrance. NMR studies suggest that the G14R mutation induces a local structural alteration in aSyn, and lower thioflavin T binding in in vitro fibrillization assays. Interestingly, the G14R aSyn fibers display different fibrillar morphologies as revealed by cryo-electron microscopy. Cellular studies of the G14R variant revealed increased inclusion formation, enhanced membrane association, and impaired dynamic reversibility of serine-129 phosphorylation. Summary: The atypical neuropathological features observed, which are reminiscent of those observed for the G51D aSyn variant, suggest a causal role of the SNCA variant with a distinct clinical and pathological phenotype, which is further supported by the properties of the mutant aSyn, compatible with the strain hypothesis of proteinopathies.

Exploring wine yeast natural biodiversity to select strains with enological traits adapted to climate change.

Wine is widely consumed throughout the world and represents a significant financial market, but production faces increasing challenges. While consumers progressively value more complex flavor profiles, regional authenticity, and decreased use of additives, winemakers strive for consistency among climate change, characterized by rising environmental temperatures and sun burn events. This often leads to grapes reaching phenolic maturity with higher sugar levels, and increased microbial spoilage risk. Herein, we addressed these dual concerns by investigating the use of autochthonous Saccharomyces cerevisiae strains for fermentations of grape musts resulting from these altered conditions. We characterized underexplored repositories of naturally-occurring strains isolated from different environments and geographical regions, regarding adequate enological properties (e.g., high cell growth, reduced production of H2S, ethanol and acetic acid, increased SO2 resistance, killer activity), and other less frequently investigated properties (resistance to osmotic stress, potassium and aluminium silicates and fungicides). The phenotypic data were organized in a biobank, and bioinformatic analysis grouped the strains according to their characteristics. Furthermore, we analyzed the potential of four Portuguese isolates to be used in fermentations of grape musts with high sugar levels, uncovering promising candidates. This research therefore contributes to ongoing efforts to increase sustainability and quality of wine production.

A versatile yeast model identifies the pesticides cymoxanil and metalaxyl as risk factors for synucleinopathies.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and the presence of Lewy bodies, which predominantly consist of aggregated forms of the protein alpha-synuclein (aSyn). While these aggregates are a pathological hallmark of PD, the etiology of most cases remains elusive. Although environmental risk factors have been identified, such as the pesticides dieldrin and MTPT, many others remain to be assessed and their molecular impacts are underexplored. This study aimed to identify pesticides that could enhance aSyn aggregation using a humanized yeast model expressing aSyn fused to GFP as a primary screening platform, which we validated using dieldrin. We found that the pesticides cymoxanil and metalaxyl induce aggregation of aSyn in yeast, which we confirmed also occurs in a model of aSyn inclusion formation using human H4 cells. In conclusion, our approach generated invaluable molecular data on the effect of pesticides, therefore providing insights into mechanisms associated with the onset and progression of PD and other synucleinopathies.

Intervention studies with group design targeting expressive phonology for children with developmental speech and language disorder: A systematic review and meta-analysis.

BACKGROUND: Phonological difficulties are prevalent in children with speech and/or language disorders and may hamper their later language outcomes and academic achievements. These children often form a significant proportion of speech and language therapists' caseloads. There is a shortage of information on evidence-based interventions for improving phonological skills in children and adolescents with speech and language disorder. AIMS: The aim of this systematic literature review and meta-analysis was to systematically examine the effects of different intervention approaches on speech production accuracy and phonological representation skills in children with speech and language disorders. METHODS: A preregistered systematic review (International Prospective Register of Systematic Reviews ID: CRD42017076075) adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was completed. Seven electronic databases (PubMed, Web of Science, ERIC, PsychINFO, Cochrane Library, SCOPUS and Linguistics & Language Behavior Abstracts) were searched for studies related to oral language interventions with children with developmental speech and/or language disorder (mean age ranging from 3-18 years) published between January 2006 and August 2022. The included articles reported intervention studies with a group design in which speech production accuracy was the outcome measure. Studies were appraised using the Cochrane risk of bias tool, and individual effect sizes were calculated using standardised means differences when enough data was available. A meta-analysis was conducted obtaining the average standardised mean difference d. Heterogeneity, influence of possible moderator variables and publication bias were explored. RESULTS: The 23 studies that met the inclusion criteria presented low-medium risk of bias. Nine effect sizes were obtained from seven of these studies that presented a pre-post-test with a control group design. Medium-high average effect sizes were found in phonological accuracy. Heterogeneity was found between individual effect sizes. Significant moderator variables and publication bias were not detected. CONCLUSIONS: The results of this meta-analysis indicate positive effects on speech production accuracy. Based on this review, further improvements in the quality of reporting for intervention research are required in developing the evidence base for practice. WHAT THIS PAPER ADDS: What is already known on the subject An increasing number of interventions is available for children and adolescents with developmental speech and/or language disorders. Previous reviews suggest relatively low levels of evidence of interventions having phonology as an outcome measure. What this paper adds to the existing knowledge This review and meta-analysis summarise the intervention evidence from a substantial body of group design studies, indicating positive results from a range of interventions with phonological outcomes. It highlights the need to systematically implement and replicate different intervention procedures to understand factors that will maximise positive outcomes and to grow the evidence base for best practice. What are the potential or actual clinical implications of this study? Tentative evidence is emerging for the effectiveness of various approaches in enhancing speech production accuracy skills of children and adolescents with developmental speech and/or language disorder.

Effectiveness of psychological interventions to decrease cognitive fusion in patients with chronic pain: A systematic review and meta-analysis.

OBJECTIVE: While there is sufficient evidence of Acceptance and Commitment Therapy's effectiveness in allowing patients to deal with chronic pain, the effectiveness in cognitive fusion, one of the six core components of the Psychology Flexibility Model, has yet to be established. The aim of this article is to assess whether psychological interventions decrease cognitive fusion. METHODS: The Web of Science, SCOPUS, Medline, and PsycINFO databases were searched for primary studies up to June 2024. Studies with a cognitive fusion measure in which chronic pain patients received a psychological intervention were included. A methodological quality scale was applied to the selected studies and the average effect sizes (Hedges g) were calculated. RESULTS: This review included 18 articles with 24 studies (19 pre-post/follow-up studies and five randomized control trials). Cognitive fusion decreased significantly after the intervention. The effect sizes were small/medium at post-test, g = -0.39, p < .001, 95% CI [-0.52, -0.26]; and medium at long-term follow-up, g = -0.55, p < .001, 95% CI [-0.74, -0.36]. A similar tendency was found for studies with RCTs at post-test, g = -0.61, p = .006, 95% CI [-1.05, -0.17], short-term follow-up, g = -0.79, p < .001, 95% CI [-1.18, -0.40] and long-term follow-up, g = -0.58, p = .003, 95% CI [-0.95, -0.20]). Moderator variables such as unemployment, gender, pain intensity, level of depression before the intervention, and duration and intervention modality were identified. CONCLUSION: Psychological interventions tended to decrease cognitive fusion in chronic pain patients. Nonetheless, more clinical trials are needed to establish the role of cognitive fusion in psychological flexibility.

The fungicide cymoxanil impairs respiration in Saccharomyces cerevisiae via cytochrome c oxidase inhibition.

Cymoxanil (CYM) is a widely used synthetic acetamide fungicide, but its biochemical mode of action remains elusive. Since CYM inhibits cell growth, biomass production, and respiration in Saccharomyces cerevisiae, we used this model to characterize the effect of CYM on mitochondria. We found it inhibits oxygen consumption in both whole cells and isolated mitochondria, specifically inhibiting cytochrome c oxidase (CcO) activity during oxidative phosphorylation. Based on molecular docking, we propose that CYM blocks the interaction of cytochrome c with CcO, hampering electron transfer and inhibiting CcO catalytic activity. Although other targets cannot be excluded, our data offer valuable insights into the mode of action of CYM that will be instrumental in driving informed management of the use of this fungicide.

Current and novel approaches in yeast cell death research.

The study of cell death mechanisms in fungi, particularly yeasts, has gained substantial interest in recent decades driven by the potential for biotechnological advancements and therapeutic interventions. Examples include the development of robust yeast strains for industrial fermentations and high-value compound production, novel food preservation strategies against spoilage yeasts, and the identification of targets for treating fungal infections in the clinic. In this review, we discuss a wide range of methods to characterize cellular alterations associated with yeast cell death, noting the advantages and limitations. We describe assays to monitor reversible events versus those that mark a commitment to cell death (point-of-no-return), as these distinctions are important to decipher the underlying regulatory mechanisms. Several well-known challenges remain, including the varied susceptibilities to death within a cell population and the delineation of detailed cell death mechanisms. The identification and characterization of morphologically distinct subsets of dying yeast cells within dynamic yeast populations provides opportunities to reveal novel vulnerabilities and survival mechanisms. Elucidating the intricacies of yeast regulated cell death (yRCD) will contribute to the advancement of scientific knowledge and foster breakthrough discoveries with broad-ranging implications.

Psycho-emotional intervention with parents of very preterm babies during the first year: A single-arm pilot study.

Studies of intervention programs that aim to improve the emotional state of parents of children admitted to the neonatal intensive care units (NICU) are scarce in Spain. The aims of this single-arm pilot study are to get to know the emotional profile of parents of high-risk preterm newborns, and to explore parents' patterns of emotional well-being before and after a psychological program called the Parental Empowerment Program, to increase parental readiness levels. The sample was made up of 100 parents (50 couples) who participated in the program. Measurements were taken of post-traumatic stress, depression, and resilience at 1 month and 12 months. Repeated measurements and dyadic data analyses were performed. One month after the birth of the baby and prior to the start of the program, mothers show more symptoms of stress and depression than fathers. After the intervention, both parents experienced improvements in their mood levels. The evidence obtained seems to show that high resilience levels and low post-traumatic stress symptoms are associated with reduced depression levels after implementing the program. However, the heterogeneity of the responses obtained, the observed associations between stress, resilience, and maternal depression, along with the reciprocal influence between maternal and paternal depression 1 year after the intervention, highlight the need for a more in-depth exploration of the interplay between risk and protective factors in this population. Despite the identified potential threats to validity, further work in this direction is recommended, including the implementation of clinical trials to demonstrate intervention efficacy. The adaptation of the parents' mutual emotional adjustment at each stage would allow them to participate more actively in the baby's care.

Enhancement of Acetate-Induced Apoptosis of Colorectal Cancer Cells by Cathepsin D Inhibition Depends on Oligomycin A-Sensitive Respiration.

Colorectal cancer (CRC) is a leading cause of death worldwide. Conventional therapies are available with varying effectiveness. Acetate, a short-chain fatty acid produced by human intestinal bacteria, triggers mitochondria-mediated apoptosis preferentially in CRC but not in normal colonocytes, which has spurred an interest in its use for CRC prevention/therapy. We previously uncovered that acetate-induced mitochondrial-mediated apoptosis in CRC cells is significantly enhanced by the inhibition of the lysosomal protease cathepsin D (CatD), which indicates both mitochondria and the lysosome are involved in the regulation of acetate-induced apoptosis. Herein, we sought to determine whether mitochondrial function affects CatD apoptotic function. We found that enhancement of acetate-induced apoptosis by CatD inhibition depends on oligomycin A-sensitive respiration. Mechanistically, the potentiating effect is associated with an increase in cellular and mitochondrial superoxide anion accumulation and mitochondrial mass. Our results provide novel clues into the regulation of CatD function and the effect of tumor heterogeneity in the outcome of combined treatment using acetate and CatD inhibitors.

Novel yeast-based biosensor for environmental monitoring of tebuconazole.

Due to increasing demand for high and stable crop production, human populations are highly dependent on pesticide use for growing and storing food. Environmental monitoring of these agrochemicals is therefore of utmost importance, because of their collateral effects on ecosystem and human health. Even though most current-use analytical methods achieve low detection limits, they require procedures that are too complex and costly for routine monitoring. As such, there has been an increased interest in biosensors as alternative or complementary tools to streamline detection and quantification of environmental contaminants. In this work, we developed a biosensor for environmental monitoring of tebuconazole (TEB), a common agrochemical fungicide. For that purpose, we engineered S. cerevisiae cells with a reporter gene downstream of specific promoters that are expressed after exposure to TEB and characterized the sensitivity and specificity of this model system. After optimization, we found that this easy-to-use biosensor consistently detects TEB at concentrations above 5 µg L-1 and does not respond to realistic environmental concentrations of other tested azoles, suggesting it is specific. We propose the use of this system as a complementary tool in environmental monitoring programs, namely, in high throughput scenarios requiring screening of numerous samples. KEY POINTS: • A yeast-based biosensor was developed for environmental monitoring of tebuconazole. •The biosensor offers a rapid and easy method for tebuconazole detection ≥ 5 µg L-1. •The biosensor is specific to tebuconazole at environmentally relevant concentrations.

The Methodological Quality Scale (MQS) for intervention programs: validity evidence.

Introduction: A wide variety of instruments are used when assessing the methodological quality (MQ) of intervention programs. Nevertheless, studies on their metric quality are often not available. In order to address this shortcoming, the methodological quality scale (MQS) is presented as a simple and useful tool with adequate reliability, validity evidence, and metric properties. Methods: Two coders independently applied the MQS to a set of primary studies. The number of MQ facets was determined in parallel analyses before performing factor analyses. For each facet of validity obtained, mean and standard deviation are presented jointly with reliability and average discrimination. Additionally, the validity facet scores are interpreted based on Shadish, Cook, and Campbell's validity model. Results and discussion: An empirical validation of the three facets of the MQ (external, internal, and construct validity) and the interpretation of the scores were obtained based on a theoretical framework. Unlike other existing scales, MQS is easy to apply and presents adequate metric properties. In addition, MQ profiles can be obtained in different areas of intervention using different methodologies and proves useful for both researchers doing meta-analysis and for evaluators and professionals designing a new intervention.

Methodological procedure based on quantitizing/liquefying: a case study to assess work climate in an emergency department.

Introduction: In the assessment of health organizations, results-based indicators are mainly used, with no consideration of internal work dynamics. This type of assessment forfeits much of the rich, useful information needed to make decisions on improving the organization. In order to address this, a rigorous procedure based on mixed methods is laid out here on gathering, analyzing, and interpreting data associated with the implementation process. Methods: A 55-year-old doctor was selected at random from among the staff who volunteered to be interviewed at the emergency department at a public hospital located in southern Spain for an interview. Qualitative data obtained from the in-depth interview (indirect observation) were progressively systematized (liquefied and quantitized) based on a theoretical framework until a code matrix was obtained, without losing or distorting any information. Afterwards, data quality was controlled using Cohen's kappa (κ) coefficient. A quantitative polar coordinate analysis was then carried out using the free software HOISAN (v. 1.6.3.3) to obtain robust results, vectorizing the relationships between codes and specifying whenever such relationships were statistically significant (and if they resulted in behavior activation or inhibition). Finally, a supplementary quantitative and qualitative assessment was carried out. Results and discussion: The proposed method was applied to the needs assessment of teams in order to evaluate that work climate in the hospital's emergency department Health Services of a hospital. Data quality control yielded an adequate result (κ = 0.82). Significant activation and inhibition of behaviors occurred, both prospectively and retrospectively. For instance, We seek to understand the needs of our clients and We readily adapt to new circumstances showed a significant activation (vector length = 3.43, p < 0.01) both prospectively (Zsum = 0.48) and retrospectively (Zsum = 3.4).An adequate method to obtain detailed information about group dynamics in a work environment is presented, based on an in-depth interview. Practical applications for implementations to improve the functioning of organizations are presented.

Monitoring yeast regulated cell death: trespassing the point of no return to loss of plasma membrane integrity.

Acetic acid and hydrogen peroxide are the most common stimuli to induce apoptosis in yeast. The initial phase of this cell death process is characterized by the maintenance of plasma membrane integrity in cells that had already lost their viability. As loss of plasma membrane integrity is typically assessed by staining with propidium iodide (PI) after exposure of cells to a stimulus and cell viability is determined 48 h after plating, the percentage of cells with compromised plasma membrane integrity and c.f.u. counts often do not correlate. Herein, we developed a simple method to explore at what point after an apoptotic stimulus and plating cells do non-viable cells die as result of plasma membrane disruption, i.e., when cells surpass the point-of-no-return and undergo a secondary necrosis. The method consisted in washing cells and re-suspending them in stimulus-free medium after acetic acid and hydrogen peroxide treatments, to mimic transfer to plating, and then assessing plasma membrane integrity through PI staining. We show that, after the stimuli are removed, cells that had lost proliferative capacity but still maintained plasma membrane integrity continue the cell death process and later lose plasma membrane integrity when progressing to secondary necrosis. After exposure to hydrogen peroxide, cells undergo secondary necrosis preceded by Nhp6Ap-GFP cytosolic localization, in contrast to acetic acid exposure, where Nhp6Ap-GFP cytosolic localization mainly occurs simultaneously with an earlier emergence of secondary necrosis. In conclusion, the developed method allows monitoring the irreversible loss of plasma membrane integrity of dying apoptotic cells after the point-of-no-return is trespassed, and better characterize the process of secondary necrosis after apoptosis.

Emotional Self-Regulation in Everyday Life: A Systematic Review.

Emotional self-regulation in childhood and adolescence constitutes a growing interest in the scientific community, highlighting in recent years the need to observe its development in their daily life. Therefore, the objective of this systematic review is to characterize publications referring to the development of emotional self-regulation of people under 18 years-old, in natural contexts. Based on the PRISMA guidelines, searches are carried out in the Web of Science, Scopus and PsycINFO databases, and in Google Scholar until May 2020. After reviewing the full text of 376 publications, 14 works are selected that are observed in their extrinsic, substantive and methodological characteristics based on the GREOM and MQCOM guidelines, by two independent evaluators. Most of the studies correspond to the last 20 years, increasing the interest in observing older children, in interaction with adults and/or in different cultures. They apply mixed methodologies, not always ascribing to a low intensity design. Strengths are observed regarding the collection and analysis of the quality of the data; and weaknesses related to the failure to record the duration and sequence of behaviors, highlighting the use of guidelines as guides for future research.

Acetic acid triggers cytochrome c release in yeast heterologously expressing human Bax.

Proteins of the Bcl-2 protein family, including pro-apoptotic Bax and anti-apoptotic Bcl-xL, are critical for mitochondrial-mediated apoptosis regulation. Since yeast lacks obvious orthologs of Bcl-2 family members, heterologous expression of these proteins has been used to investigate their molecular and functional aspects. Active Bax is involved in the formation of mitochondrial outer membrane pores, through which cytochrome c (cyt c) is released, triggering a cascade of downstream apoptotic events. However, when in its inactive form, Bax is largely cytosolic or weakly bound to mitochondria. Given the central role of Bax in apoptosis, studies aiming to understand its regulation are of paramount importance towards its exploitation as a therapeutic target. So far, studies taking advantage of heterologous expression of human Bax in yeast to unveil regulation of Bax activation have relied on the use of artificial mutated or mitochondrial tagged Bax for its activation, rather than the wild type Bax (Bax α). Here, we found that cell death could be triggered in yeast cells heterologoulsy expressing Bax α with concentrations of acetic acid that are not lethal to wild type cells. This was associated with Bax mitochondrial translocation and cyt c release, closely resembling the natural Bax function in the cellular context. This regulated cell death process was reverted by co-expression with Bcl-xL, but not with Bcl-xLΔC, and in the absence of Rim11p, the yeast ortholog of mammalian GSK3ß. This novel system mimics human Bax α regulation by GSK3ß and can therefore be used as a platform to uncover novel Bax regulators and explore its therapeutic modulation.

Saccharomyces cerevisiae Cells Lacking the Zinc Vacuolar Transporter Zrt3 Display Improved Ethanol Productivity in Lignocellulosic Hydrolysates.

Yeast-based bioethanol production from lignocellulosic hydrolysates (LH) is an attractive and sustainable alternative for biofuel production. However, the presence of acetic acid (AA) in LH is still a major problem. Indeed, above certain concentrations, AA inhibits yeast fermentation and triggers a regulated cell death (RCD) process mediated by the mitochondria and vacuole. Understanding the mechanisms involved in AA-induced RCD (AA-RCD) may thus help select robust fermentative yeast strains, providing novel insights to improve lignocellulosic ethanol (LE) production. Herein, we hypothesized that zinc vacuolar transporters are involved in vacuole-mediated AA-RCD, since zinc enhances ethanol production and zinc-dependent catalase and superoxide dismutase protect from AA-RCD. In this work, zinc limitation sensitized wild-type cells to AA-RCD, while zinc supplementation resulted in a small protective effect. Cells lacking the vacuolar zinc transporter Zrt3 were highly resistant to AA-RCD, exhibiting reduced vacuolar dysfunction. Moreover, zrt3Δ cells displayed higher ethanol productivity than their wild-type counterparts, both when cultivated in rich medium with AA (0.29 g L-1 h-1 versus 0.11 g L-1 h-1) and in an LH (0.73 g L-1 h-1 versus 0.55 g L-1 h-1). Overall, the deletion of ZRT3 emerges as a promising strategy to increase strain robustness in LE industrial production.

Predictive Factors of Mental Health in Survivors of Intimate Partner Violence in Chile.

Studies about violence against women specific to the Chilean population are scarce. As a result, government treatment programs lack a local perspective. Predictor variables were analyzed in the mental health of Chilean women who have survived intimate partner abuse. Two hundred and two women who made regular visits to public Women's Centers participated in the study; on average, they had survived 11 years of abuse. Logistic regression analyses were conducted to determine what variable/s in the history of violence best predicted the mental health variables. Among other protective factors, an increase in both resilience and the time since the last violent episode yielded a reduction in levels of general psychological distress (B = -1.836, p < .001 and B = 1.117, p < .001 respectively), post-traumatic stress disorder (B = -1.243, p = .002 and B = 1.221, p < .001 respectively), and depression (B = -1.822, p < .001 and B = 1.433, p < .001 respectively). The study also noted risk factors such as a high level of additional stressors, which in turn led to increased levels of general psychological distress (B = 1.007, p = .005), post-traumatic stress disorder (B = 0.928, p = .013), and depression (B = 1.061, p = .016). The Women's Center is the place where women feel most supported. To improve the effectiveness of treatments at these centers and aid in the recovery of women who have suffered from intimate partner violence, the predictive factors significantly related to mental health should be taken into account. This means prioritizing cases where the last episode of violence was more recent, addressing additional stressors, and promoting resilience.

The PALliative MUlticenter Study in Intensive Care (PalMuSIC). Results From a Multicenter Study Addressing Frailty and Palliative Care Interventions in Intensive Care Units in Portugal.

Objective: Frailty is a clinically recognizable state of increased vulnerability common in critical medicine. When underrecognized, it may lead to invasive treatments that do not serve the patients' best interest. Our aim was to evaluate the use of both palliative care consultation and invasive interventions in frail patients admitted to Intensive Care Units in Portugal. Methods: This was a prospective, observational study. All consecutive adult patients admitted for more than 24 h, over a 15-day period were enrolled. Twenty-three Portuguese Intensive Care Units were included. Informed consent was obtained from all patients or their surrogate. The doctor and nurse in charge calculated the Clinical Frailty Score as well as the reference family member Results: A total of 335 patients were included in the study (66% male). Mean age was 63.2 ± 16.8 and SAPS II score was 41.8 ± 17.4. Mean Clinical Frailty Score value was 3.5 ± 1.7. Frailty prevalence (mean score ≥ 5) was 20.9%. Frail patients were offered organ support therapy (64,3% invasive mechanical ventilation; 24,3% renal replacement therapy; 67,1% vasopressors) more often than non-frail patients. Nevertheless, limitation of therapeutic effort or a do not resuscitate order (p < 0.001) were more common in frail patients. Mortality rate by 6 months was higher among frail patients (50% vs. 32.3%, p < 0.001). Palliative Care was offered to only 15% of frail patients (3.9% overall). Conclusions: The authors suggest that palliative care should be universally consulted once frailty is identified in critical patients.