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The eukaryotic cytosolic Fe-S protein assembly (CIA) machinery inserts iron-sulfur (Fe-S) clusters into cytosolic and nuclear proteins. In the final maturation step, the Fe-S cluster is transferred to the apo-proteins by the CIA-targeting complex (CTC). However, the molecular recognition determinants of client proteins are unknown. We show that a conserved [LIM]-[DES]-[WF]-COO- tripeptide is present at the C-terminus of more than a quarter of clients or their adaptors. When present, this targeting complex recognition (TCR) motif is necessary and sufficient for binding to the CTC in vitro and for directing Fe-S cluster delivery in vivo. Remarkably, fusion of this TCR signal enables engineering of cluster maturation on a nonnative protein via recruitment of the CIA machinery. Our study advances our understanding of Fe-S protein maturation and paves the way for bioengineering novel pathways containing Fe-S enzymes.
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Proteínas Ferro-Enxofre , Humanos , Proteínas Ferro-Enxofre/metabolismo , Citosol/metabolismo , Proteínas Nucleares/metabolismo , Ferro/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismoRESUMO
BACKGROUND: Lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) significantly impact quality of life among older men. Despite the prevalent use of the American Urological Association Symptom Index (AUA-SI) for BPH, this measure overlooks key symptoms such as pain and incontinence, underscoring the need for more comprehensive patient-reported outcome (PRO) tools. This study aims to integrate enhanced PROs into routine clinical practice to better capture the spectrum of LUTS, thereby improving clinical outcomes and patient care. METHODS: This prospective observational study will recruit men with LUTS secondary to BPH aged ≥ 50 years from urology clinics. Participants will be stratified into medical and surgical management groups, with PRO assessments scheduled at regular intervals to monitor LUTS and other health outcomes. The study will employ the LURN Symptom Index (SI)-29 alongside the traditional AUA-SI and other non-urologic PROs to evaluate a broad range of symptoms. Data on comorbidities, symptom severity, and treatment efficacy will be collected through a combination of electronic health records and PROs. Analyses will focus on the predictive power of these tools in relation to symptom trajectories and treatment responses. Aims are to: (1) integrate routine clinical tests with PRO assessment to enhance screening, diagnosis, and management of patients with BPH; (2) examine psychometric properties of the LURN SIs, including test-retest reliability and establishment of clinically meaningful differences; and (3) create care-coordination recommendations to facilitate management of persistent symptoms and common comorbidities measured by PROs. DISCUSSION: By employing comprehensive PRO measures, this study expects to refine symptom assessment and enhance treatment monitoring, potentially leading to improved personalized care strategies. The integration of these tools into clinical settings could revolutionize the management of LUTS/BPH by providing more nuanced insights into patient experiences and outcomes. The findings could have significant implications for clinical practices, potentially leading to updates in clinical guidelines and better health management strategies for men with LUTS/BPH. TRIAL REGISTRATION: This study is registered in ClinicalTrials.gov (NCT05898932).
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Sintomas do Trato Urinário Inferior , Medidas de Resultados Relatados pelo Paciente , Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/complicações , Hiperplasia Prostática/terapia , Estudos Prospectivos , Sintomas do Trato Urinário Inferior/terapia , Sintomas do Trato Urinário Inferior/etiologia , Tomada de Decisão Clínica/métodos , Pessoa de Meia-Idade , IdosoRESUMO
BACKGROUND: Alzheimer's disease and related dementias (ADRD) are among the most feared age-related conditions. The aim of this study was to evaluate a brief psychological intervention to promote adaptive coping in older adults experiencing heightened fear of ADRD and investigate positive downstream effects on health-related secondary outcomes, including frequency of reported memory failures, psychosocial functioning, and quality of life. METHODS: Eighty-one older adults were recruited and randomized into REFRAME or active control intervention arms. Both groups received psycho-education and training in mindful monitoring of fears related to ADRD. The REFRAME group received an additional behavioral activation component intended to disrupt maladaptive avoidant coping (i.e., avoidance) strategies. Both groups completed 3-weeks of intervention exercises with accompanying questionnaires (baseline, mid- and post-intervention and 4-week follow-up). RESULTS: Adherence was strong (> 75%). We observed a significant reduction in ADRD-related fear and avoidance in both groups. Significant reductions were also observed for frequency of self-reported memory failures, anxiety, and depression. Depression was significantly reduced in the REFRAME group compared to the control group. Significant increases in participants' ability to participate in social activities and well-being were also observed. CONCLUSIONS: Findings suggest that a brief psychological intervention can mitigate ADRD-related fears and avoidant coping in older adults, and that benefits extend to broader health-related outcomes including anxiety, depression, social functioning, and well-being. Addressing ADRD-related fear has implications for healthy aging and risk reduction, as individuals may be more likely to engage in activities that are protective against ADRD but were previously avoided. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04821960 .
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Doença de Alzheimer , Qualidade de Vida , Humanos , Idoso , Participação Social , Doença de Alzheimer/psicologia , Medo/psicologia , Transtornos da Memória/prevenção & controleRESUMO
Supercritical CO2 (sCO2) removes water from brine held in pumice stone at levels well above the solubility of water in sCO2. The higher water removal results from a combination of passive emulsification of water in sCO2 and viscous fingering of sCO2 through the saturated pumice. This leads to higher levels of salt deposition than that expected from solubility considerations alone. These deposits could impact the injectivity of sCO2 as well as its movement in the subsurface. The finding that the water concentration in sCO2 is not necessarily capped at the solubility limit should influence the parametrization of injection models.
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INTRODUCTION: South Asian (SA) and East Asian (EA) older adults represent the fastest-growing racial/ethnic groups of Americans at risk for dementia. While recruiting older SA adults into a brain health study, we encountered unexpected hesitancy toward structural brain magnetic resonance imaging (MRI) analysis and stigmatizing attitudes related to internal locus of control (LoC) for future dementia risks. We hypothesized that support for MRI-related research was influenced by these attitudes as well as personal MRI experience, perceived MRI safety, and concerns for personal risk for future dementia/stroke. METHODS: We developed a brief cross-sectional survey to assess older adults' MRI experiences and perceptions, desire to learn of six incidental findings of increasing impact on health, and attitudes related to dementia (including LoC) and research participation. We recruited a convenience sample of 256 respondents (74% reporting as 50+) from the New Jersey/New York City area to complete the survey (offered in English, Chinese, Korean, and Spanish) and modeled the proportional odds (PO) for favorable attitudes toward research activities. RESULTS: Seventy-seven SA and 84 EA respondents were analyzed alongside 95 White, Black, or Hispanic adults. White (PO = 2.54, p = 0.013) and EA (PO = 2.14, p = 0.019) respondents were both more likely than SA respondents to endorse healthy volunteers' participation in research, and the difference between White and SA respondents was mediated by the latter's greater internal LoC for dementia risks. EA respondents had more worries for future dementia/stroke than SA respondents (p = 0.006) but still shared SA respondents' lower wish (measured by proportion of total) to learn of incidental MRI findings. DISCUSSION: SA-and EA compared to SA-older adults had low desire to learn of incidental MRI findings but had different attitudes toward future dementia/stroke risks. A culturally appropriate protocol to disclose incidental MRI findings may improve SA and EA participation in brain health research. Highlights: Older Asian Americans have limited interest in incidental findings on research MRISouth Asians are most likely to attribute dementia to people's own behaviorsSouth Asians' attitudes mediate lower support for healthy volunteers in researchSouth and East Asians differ in dementia worries and research-related attitudes.
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Background: Lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) significantly impact quality of life among older men. Despite the prevalent use of the American Urological Association Symptom Index (AUA-SI) for BPH, this measure overlooks key symptoms such as pain and incontinence, underscoring the need for more comprehensive patient-reported outcome (PRO) tools. This study aims to integrate enhanced PROs into routine clinical practice to better capture the spectrum of LUTS, thereby improving clinical outcomes and patient care. Methods: This prospective observational study will recruit men with LUTS secondary to BPH aged ≥ 50 years from urology clinics. Participants will be stratified into medical and surgical management groups, with PRO assessments scheduled at regular intervals to monitor LUTS and other health outcomes. The study will employ the LURN Symptom Index (SI)-29 alongside the traditional AUA-SI and other non-urologic PROs to evaluate a broad range of symptoms. Data on comorbidities, symptom severity, and treatment efficacy will be collected through a combination of electronic health records and PROs. Analyses will focus on the predictive power of these tools in relation to symptom trajectories and treatment responses. Aims are to: (1) integrate routine clinical tests with PRO assessment to enhance screening, diagnosis, and management of patients with BPH; (2) examine psychometric properties of the LURN SIs, including test-retest reliability and establishment of clinically meaningful differences; and (3) create care-coordination recommendations to facilitate management of persistent symptoms and common comorbidities measured by PROs. Discussion: By employing comprehensive PRO measures, this study expects to refine symptom assessment and enhance treatment monitoring, potentially leading to improved personalized care strategies. The integration of these tools into clinical settings could revolutionize the management of LUTS/BPH by providing more nuanced insights into patient experiences and outcomes. The findings could have significant implications for clinical practices, potentially leading to updates in clinical guidelines and better health management strategies for men with LUTS/BPH. Trial registration: This study is registered in ClinicalTrials.gov (NCT05898932).
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Multiple studies across a variety of scientific disciplines have shown that the number of times that a paper is shared on Twitter (now called X) is correlated with the number of citations that paper receives. However, these studies were not designed to answer whether tweeting about scientific papers causes an increase in citations, or whether they were simply highlighting that some papers have higher relevance, importance or quality and are therefore both tweeted about more and cited more. The authors of this study are leading science communicators on Twitter from several life science disciplines, with substantially higher follower counts than the average scientist, making us uniquely placed to address this question. We conducted a three-year-long controlled experiment, randomly selecting five articles published in the same month and journal, and randomly tweeting one while retaining the others as controls. This process was repeated for 10 articles from each of 11 journals, recording Altmetric scores, number of tweets, and citation counts before and after tweeting. Randomization tests revealed that tweeted articles were downloaded 2.6-3.9 times more often than controls immediately after tweeting, and retained significantly higher Altmetric scores (+81%) and number of tweets (+105%) three years after tweeting. However, while some tweeted papers were cited more than their respective control papers published in the same journal and month, the overall increase in citation counts after three years (+7% for Web of Science and +12% for Google Scholar) was not statistically significant (p > 0.15). Therefore while discussing science on social media has many professional and societal benefits (and has been a lot of fun), increasing the citation rate of a scientist's papers is likely not among them.
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Disciplinas das Ciências Biológicas , Mídias Sociais , Humanos , Bibliometria , Fator de Impacto de RevistasRESUMO
Introduction: Alzheimer's disease and related dementias (ADRD) are among the most feared conditions. However, research around ADRD-specific fear and avoidance behaviors is lacking. Here, we validated a novel measure of fear and avoidance specific to memory loss, the Fear and Avoidance of Memory Loss (FAM) scale, and examined associations between fear avoidance and psychosocial functioning in older adults. Methods: We assessed FAM Scale internal reliability and concurrent validity, and candidate subscales across two samples (total N = 813). We then examined associations between fear avoidance and memory performance, anxiety, depressive symptoms, sleep, social functioning, and quality of life. Results: We identified two subscales: fear and avoidance, which yielded strong psychometric validity. Higher fear was associated with memory failures and sleep disturbance. Higher avoidance was associated with memory failures, poorer verbal memory, reduced social functioning, and quality of life. Discussion: We present the first measure of fear avoidance specific to memory loss. We propose that targeting fear avoidance can promote ADRD risk reduction and resiliency.
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Iron-sulfur clusters are essential for life and defects in their biosynthesis lead to human diseases. The mechanism of cluster assembly and delivery to cytosolic and nuclear client proteins via the cytosolic iron-sulfur cluster assembly (CIA) pathway is not well understood. Here we report cryo-EM structures of the HEAT-repeat protein Met18 from Saccharomyces cerevisiae, a key component of the CIA targeting complex (CTC) that identifies cytosolic and nuclear client proteins and delivers a mature iron-sulfur cluster. We find that in the absence of other CTC proteins, Met18 adopts tetrameric and hexameric states. Using mass photometry and negative stain EM, we show that upon the addition of Cia2, these higher order oligomeric states of Met18 disassemble. We also use pulldown assays to identify residues of critical importance for Cia2 binding and recognition of the Leu1 client, many of which are buried when Met18 oligomerizes. Our structures show conformations of Met18 that have not been previously observed in any Met18 homolog, lending support to the idea that a highly flexible Met18 may be key to how the CTC is able to deliver iron-sulfur clusters to client proteins of various sizes and shapes, i.e. Met18 conforms to the dimensions needed.
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Temperatura Alta , Proteínas Ferro-Enxofre , Humanos , Proteínas Ferro-Enxofre/química , Citosol/metabolismo , Proteínas Nucleares/metabolismo , Saccharomyces cerevisiae/metabolismo , Ferro/metabolismo , Enxofre/metabolismoRESUMO
BACKGROUND: A high rate of COVID-19 vaccination is critical to reduce morbidity and mortality related to infection and to control the COVID-19 pandemic. Understanding the factors that influence vaccine confidence can inform policies and programs aimed at vaccine promotion. We examined the impact of health literacy on COVID-19 vaccine confidence among a diverse sample of adults living in two major metropolitan areas. METHODS: Questionnaire data from adults participating in an observational study conducted in Boston and Chicago from September 2018 through March 2021 were examined using path analyses to determine whether health literacy mediates the relationship between demographic variables and vaccine confidence, as measured by an adapted Vaccine Confidence Index (aVCI). RESULTS: Participants (N = 273) were on average 49 years old, 63 % female, 4 % non-Hispanic Asian, 25 % Hispanic, 30 % non-Hispanic white, and 40 % non-Hispanic Black. Using non-Hispanic white and other race as the reference category, Black race and Hispanic ethnicity were associated with lower aVCI (-0.76, 95 % CI -1.00 to -0.50; -0.52, 95 % CI -0.80 to -0.27, total effects from a model excluding other covariates). Lower education was also associated with lower aVCI (using college or more as the reference, -0.73 for 12th grade or less, 95 % CI -0.93 to -0.47; -0.73 for some college/associate's/technical degree, 95 % CI -1.05 to -0.39). Health literacy partially mediated these effects for Black and Hispanic participants and those with lower education (indirect effects -0.19 and -0.19 for Black race and Hispanic ethnicity; 0.27 for 12th grade or less; -0.15 for some college/associate's/technical degree). CONCLUSIONS: Lower levels of education, Black race, and Hispanic ethnicity were associated with lower scores on health literacy, which in turn were associated with lower vaccine confidence. Our findings suggest that efforts to improve health literacy may improve vaccine confidence, which in turn may improve vaccination rates and vaccine equity. CLINICAL TRIALS NUMBER: NCT03584490.
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Vacinas contra COVID-19 , COVID-19 , Letramento em Saúde , Vacinação , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Negro ou Afro-Americano , Boston/epidemiologia , Chicago/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias/prevenção & controle , Hispânico ou Latino , Brancos , Vacinação/psicologiaRESUMO
The eukaryotic cytosolic Fe-S protein assembly (CIA) machinery inserts iron-sulfur (Fe-S) clusters into cytosolic and nuclear proteins. In the final maturation step, the Fe-S cluster is transferred to the apo-proteins by the CIA-targeting complex (CTC). However, the molecular recognition determinants of client proteins are unknown. We show that a conserved [LIM]-[DES]-[WF]-COO- tripeptide present at the C-terminus of clients is necessary and sufficient for binding to the CTC in vitro and directing Fe-S cluster delivery in vivo. Remarkably, fusion of this TCR (target complex recognition) signal enables engineering of cluster maturation on a non-native protein via recruitment of the CIA machinery. Our study significantly advances our understanding of Fe-S protein maturation and paves the way for bioengineering applications.
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INTRODUCTION: South Asian (SA) and East Asian (EA) older adults represent the fastest growing group of Americans at risk for dementia, but their participation in aging and dementia research has been limited. While recruiting healthy SA older adults into a brain health study, we encountered unexpected hesitancy towards structural brain MRI analysis along with some stigmatizing attitudes related to internal locus of control (LoC) for future dementia risks. We hypothesized that support for MRI-related research was influenced by these attitudes as well as one's own MRI experience, perceived MRI safety, and concerns for one's own risks for future dementia/stroke. METHODS: We developed a brief cross-sectional survey to assess older adults' MRI experiences and perceptions, desire to learn of six incidental findings of increasing health implications, and attitudes related to dementia as well as research participation. We recruited a convenience sample of 256 respondents (74% reporting as 50+) from the New Jersey/New York City area to complete the survey, and modeled the proportional odds (P.O.) for pro-research attitudes. RESULTS: 77 SA and 84 EA respondents were analyzed with 95 non-Asian adults. White (P.O.=2.54, p=0.013) and EA (P.O.=2.14, p=0.019) respondents were both more likely than SA respondents to endorse healthy volunteers' participation in research, and the difference between White and SA respondents was mediated by the latter's greater internal LoC for dementia risks. EA respondents had more worries for future dementia/stroke than SA respondents (p=0.006), but still shared SA respondents' low desire to learn of incidental MRI findings. DISCUSSION: SA and EA older adults had different attitudes towards future dementia/stroke risks, but shared a low desire to learn of incidental MRI findings. A culturally-appropriate protocol to disclose incidental MRI findings may improve SA and EA participation in brain health research.
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We sought to analyze the relationship between health literacy, confidence in COVID-19 vaccines, and self-reported vaccination. We hypothesized that the relationship between health literacy and vaccination would be mediated by vaccine confidence. We recruited (N = 271) English- and Spanish-speaking adults in Boston and Chicago from September 2018 to September 2021. We performed a probit mediation analysis to determine if confidence in COVID-19 vaccines and health literacy predicted self-reported vaccination. We hypothesized that the relationship between health literacy and vaccination would be mediated by vaccine confidence. Participants were on average 50 years old, 65% female, 40% non-Hispanic Black, 25% Hispanic, and 30% non-Hispanic White; 231 (85%) reported at least one COVID-19 vaccination. A higher mean vaccine confidence score (t = -7.9, p < 0.001) and higher health literacy (t = -2.2, p = 0.03) were associated with vaccination, but only vaccine confidence predicted vaccination in a multivariate model. Vaccine confidence mediated the relationship between health literacy and COVID-19 vaccination (mediated effects: 0.04; 95% CI [0.02, 0.08]). We found that using a simple tool to measure vaccine confidence identified people who declined or delayed COVID-19 vaccination in a diverse sample of adults with varying levels of health literacy. Simple short survey tools can be useful to identify people who may benefit from vaccine promotion efforts and evidence-based communication strategies.
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BACKGROUND: Dementia is the most feared disease associated with aging. Prolonged fears about memory loss and dementia can have harmful consequences even in the absence of cognitive decline. Fear of dementia is associated with poorer health outcomes and psychological well-being and increased memory failures in older adults. OBJECTIVE: We will conduct a randomized controlled trial to determine the feasibility of a tailored, web-based mindfulness program to reduce fear of memory loss and increase quality of life in older adults experiencing heightened fear. METHODS: Eighty participants will be recruited and divided into 2 groups (40 in each group). One group will receive psychoeducation plus mindfulness training. A second group will receive psychoeducation, mindfulness training, and additional modules targeting maladaptive behavioral avoidance (ie, social and cognitive withdrawal). RESULTS: Our recent etiological model posits that maladaptive behavioral avoidance strategies critically underlie psychosocial dysfunction associated with fear of memory loss. Thus, we predict better outcomes in the second group, including reduced fear of memory loss (primary outcome), Alzheimer disease, anxiety, and subjective memory failures, and increased quality of life (secondary outcomes). Outcome measures will be applied at 5 time points (before, baseline, interim, and after the intervention, and at 3-month follow-up). Data will be analyzed using mixed models and correlations. CONCLUSIONS: Results from this study will contribute to the current literature on dementia-related fear and improve our understanding of how to effectively address and reduce these fears. TRIAL REGISTRATION: ClinicalTrials.gov NCT04821960; https://clinicaltrials.gov/ct2/show/NCT04821960. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/30514.
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Often perceived as environmentally benign, 'green' renewable energy technologies have ecological costs that are often overlooked, especially those occurring below the waterline. After briefly discussing the impacts of hydropower on freshwater and marine organisms, we focus this review on the impacts of marine renewable energy devices (MREDs) on underwater marine organisms, particularly offshore wind farms and marine energy converters (e.g., tidal turbines). We consider both cumulative impacts and synergistic interactions with other anthropogenic pressures, using offshore wind farms and the Taiwanese white dolphin (Sousa chinensis taiwanensis) as an example. While MREDs undoubtedly can help mitigate climate change, variability in the sensitivity of different species and ecosystems means that rigorous case-by-case assessments are needed to fully comprehend the consequences of MRED use.
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Ecossistema , Fontes Geradoras de Energia , Organismos Aquáticos , Energia Renovável , VentoRESUMO
The cytosolic iron-sulfur cluster assembly (CIA) system biosynthesizes iron-sulfur (FeS) cluster cofactors for cytosolic and nuclear proteins. The yeast Cia2 protein is the central component of the targeting complex which identifies apo-protein targets in the final step of the pathway. Herein, we determine that Cia2 contains five conserved motifs distributed between an intrinsically disordered N-terminal domain and a C-terminal domain of unknown function 59 (DUF59). The disordered domain is dispensible for binding the other subunits of the targeting complex, Met18 and Cia1, and the apo-target Rad3 in vitro. While in vivo assays reveal that the C-terminal domain is sufficient to support viability, several phenotypic assays indicate that deletion of the N-terminal domain negatively impacts CIA function. We additionally establish that Glu208, located within a conserved motif found only in eukaryotic DUF59 proteins, is important for the Cia1-Cia2 interaction in vitro. In vivo, E208A-Cia2 results in a diminished activity of the cytosolic iron sulfur cluster protein, Leu1 but only modest effects on hydroxyurea or methylmethane sulfonate sensitivity. Finally, we demonstrate that neither of the two highly conserved motifs of the DUF59 domain are vital for any of Cia2's interactions in vitro yet mutation of the DPE motif in the DUF59 domain results in a nonfunctional allele in vivo. Our observation that four of the five highly conserved motifs of Cia2 are dispensable for targeting complex formation and apo-target binding suggests that Cia2 is not simply a protein-protein interaction mediator but it likely possesses an additional, currently cryptic, function during the final cluster insertion step of CIA.
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Proteínas Ferro-Enxofre/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Sequência de Aminoácidos , Sítios de Ligação/genética , Citosol/metabolismo , Proteínas Ferro-Enxofre/química , Proteínas Ferro-Enxofre/genética , Mutação , Ligação Proteica , Domínios Proteicos , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genéticaRESUMO
Resumen Introducción: El delírium es un síndrome neuropsiquiátrico de etiología multifactorial que se presenta de forma frecuente en el adulto mayor hospitalizado. En Santander no hay estudios que describan su incidencia y factores epidemiológicos asociados. Objetivo: Evaluar la incidencia de delírium, características clínicas según el tipo, mortalidad a 30 días de hospitalización y complicaciones asociadas al delírium, en pacientes adultos mayores de 65 años hospitalizados en un departamento del nororiente colombiano. Materiales y métodos: Se incluyeron pacientes ≥ 65 años hospitalizados en sala general de la Clínica FOSCAL. Se excluyeron pacientes con delírium al ingreso, hospitalizados en unidad de cuidado crítico, intubación orotraqueal, Glasgow <8/15 y con limitación para evaluar el delírium de forma adecuada. Resultados: De 492 pacientes hospitalizados con edad promedio de 75 años, la incidencia acumulada fue de 9,3%; con mayor porcentaje en mujeres (63%) y en ≥ 85 años (31,5%). Se evidenció una asociación con mayor estancia hospitalaria (11.0 vs 7.1 días, p <0.05), un mayor deterioro funcional evaluado por escala Barthel y riesgo de mortalidad (HR:2.9 IC95%: 2.1-3.4). El sexo masculino, el estado cognitivo normal, índice de Barthel ≥ 60 y estado nutricional normal fueron factores protectores. Conclusiones: La incidencia de delirium en la población del oriente colombiano tuvo una incidencia similar que a nivel mundial. Se asoció con mayor estancia hospitalaria, declinación funcional y mortalidad. Aplicando escalas de tamizado cognitivo, funcional y nutricional se podrían identificar los pacientes con mayor vulnerabilidad para desarrollo de delirium. MÉD.UIS.2021;34(1):9-17.
Abstract Introduction: Delirium is a neuropsychiatric syndrome of multifactorial etiology that occurs frequently in hospitalized older adults. There are no studies describing the incidence of delirium in Santander and its associated epidemiological factors. Objective: To assess the incidence of delirium, clinical characteristics according to type, mortality after 30 days of hospitalization and complications associated with delirium, in adult patients over 65 years hospitalized in a department in Colombian northeast. Materials and Methods: We included all hospitalized patients ≥ 65 years. We excluded patients with delirium on admission, those hospitalized in intensive care unit, with orotracheal intubation, Glasgow < 8/15, or with factors limiting the ability to assess delirium. Results: 492 hospitalized patients with an average age of 75 years were analyzed. The cumulative incidence of delirium was 9.3%. Of these patients there was a higher percentage of women (63%) and adults ≥ 85 years (31.5%). The greatest association was related to longer hospital stay (11.0 vs 7.1 days, p <0.05), functional impairment evaluated by Barthel scale, and increased risk of mortality (HR:2.9 IC95%: 2.1-3.4). Male sex, normal cognitive status, Barthel index ≥ 60 and normal nutritional status were protective factors. Conclusions: The incidence of delirium in the population of eastern Colombia was similar to the incidence worldwide. Delirium was associated with longer hospital stay, functional decline, and mortality. Applying cognitive, functional, and nutritional screening scales, it would be possible to identify patients with greater vulnerability to delirium development. MÉD.UIS.2021;34(1):9-17.
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Humanos , Idoso , Delírio , Idoso , Incidência , Tempo de InternaçãoRESUMO
Members of the RecQ family of helicases are known for their roles in DNA repair, replication, and recombination. Mutations in the human RecQ helicases, WRN and BLM, cause Werner and Bloom syndromes, which are diseases characterized by genome instability and an increased risk of cancer. While WRN contains both a helicase and an exonuclease domain, the Drosophila melanogaster homolog, WRNexo, contains only the exonuclease domain. Therefore the Drosophila model system provides a unique opportunity to study the exonuclease functions of WRN separate from the helicase. We created a null allele of WRNexo via imprecise P-element excision. The null WRNexo mutants are not sensitive to double-strand break-inducing reagents, suggesting that the exonuclease does not play a key role in homologous recombination-mediated repair of DSBs. However, WRNexo mutant embryos have a reduced hatching frequency and larvae are sensitive to the replication fork-stalling reagent, hydroxyurea (HU), suggesting that WRNexo is important in responding to replication stress. The role of WRNexo in the HU-induced stress response is independent of Rad51. Interestingly, the hatching defect and HU sensitivity of WRNexo mutants do not occur in flies containing an exonuclease-dead copy of WRNexo, suggesting that the role of WRNexo in replication is independent of exonuclease activity. Additionally, WRNexo and Blm mutants exhibit similar sensitivity to HU and synthetic lethality in combination with mutations in structure-selective endonucleases. We propose that WRNexo and BLM interact to promote fork reversal following replication fork stalling and in their absence regressed forks are restarted through a Rad51-mediated process.
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Replicação do DNA , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/enzimologia , Exonucleases/metabolismo , RecQ Helicases/metabolismo , Animais , Quebras de DNA de Cadeia Dupla , DNA Helicases/genética , DNA Helicases/metabolismo , Reparo do DNA , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Exonucleases/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Hidroxiureia , Masculino , Mutação , Rad51 Recombinase/genética , Rad51 Recombinase/metabolismo , RecQ Helicases/genéticaRESUMO
Se presenta el caso de un paciente de 23 meses de edad que desarrolló parálisis facial unilateral secundaria a Enfermedad de Lyme sin síntomas otológicos previos. El caso se presentó en Colombia, considerada un área no endémica.
The paper presents the case of a 23 months old child who developed an unilateral facial paralysis secondary to Lyme Disease without previous otologic symptoms. Colombia is not considered an endemic area.
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La lepra, o enfermedad de Hansen, es una afección causada por el Mycobacterium leprae, cuyas manifestaciones clínicas varían entre dos polos, lepromatoso y tuberculoide, pudiéndose encontrar en toda la extensión corporal, incluyendo la larínge. La entidad es rara, pero en Colombia existen focos reconocidos, y dentro de la evaluación de pacientes con lesiones granulomatosas o síntomas laríngeos, con nexos epidemiológicos, debe sospecharse y diagnosticarse apropiadamente, para evitar secuelas irreversibles. Presentamos el caso de un paciente de 28 años con cuadro de disfonía, voz apagada y disnea progresiva, asociado a manifestaciones nasales y cutáneas de tres años de evolución, correspondientes a infección por Mycobacterium leprae...
Leprosy or Hansens Disease is a condition caused by Mycobacterium leprae, which clinical presentations may vary between two poles: lepromatous and tuberculoid, compromising several systems including the larynx. Leprosy is a very rare disease but in Colombia there are known places where the condition is often found, leading to the necessity of suspicion and diagnosis in patients with granulomatous lesions or laryngeal symptoms with a positive epidemiological bind, to avoid future irreversible sequels. We present a 28 years-old patient with dysphonia, muffled voice and progressive dyspnea, associated with nasal and cutaneous manifestations over 3 years, corresponding to Mycobacterium leprae infection...