Clinical effects of re-evaluating a lung SBRT failure mode and effects analysis in a radiotherapy department.

PURPOSE: The increasing complexity of radiation treatments can hinder its clinical success. This study aimed to better understand evolving risks by re-evaluating a Failure Mode and Effects Analysis (FMEA) in lung SBRT. METHODS: An experienced multidisciplinary team conducted an FMEA and made a reassessment 3 years later. A process map was developed with potential failure modes (FMs) identified. High-risk FMs and their possible causes and corrective actions were determined. The initial FMEA analysis was compared to gain a deeper perspective. RESULTS: We identified 232 FMs. The high-risk processes were plan approval, target contouring, and patient evaluation. The corrective measures were based on stricter standardization of plan approval, pre-planning peer review, and a supporting pretreatment checklist, which substantially reduced the risk priority number in the revised FMEA. In the FMEA reassessment, we observed that the increased complexity and number of patients receiving lung SBRT conditioned a more substantial presence of human factors and communication errors as causal conditions and a potential wrong dose as a final effect. CONCLUSIONS: Conducting a lung SBRT FMEA analysis has identified high-risk conditions that have been effectively mitigated in an FMEA reanalysis. Plan approval has shown to be a weak link in the process. The increasing complexity of treatments and patient numbers have shifted causal factors toward human failure and communication errors. The potential of a wrong dose as a final effect augments in this scenario. We propose that digital and artificial intelligence options are needed to mitigate potential errors in high-complexity and high-risk RT scenarios.

Prevalence of Body Dysmorphic Disorder in Private Aesthetic Clinical Settings in Four Latin American Countries: A Cross-Sectional Study.

BACKGROUND: Body dysmorphic disorder (BDD) is a psychiatric condition characterized by persistent concern with non-existent or minor defects in one's physical appearance. BDD can be difficult to identify as patients often have limited insight into the condition. OBJECTIVE: We aimed to determine the prevalence of BDD in patients presenting to private aesthetic clinical settings in four Latin American countries. METHODS: We conducted a cross-sectional study From August to October 2022 to evaluate the prevalence of BDD among 360 patients seeking nonsurgical cosmetic procedures in Chile, Mexico, Argentina, and Colombia using the Dysmorphic Concern Questionnaire (DCQ). We reported prevalence estimates for the lowest and highest previously proposed DCQ cutoff points. RESULTS: The DCQ total scores in the study population ranged from 0 to 21, with a mean total score of 5.1 ± 3.4. The prevalence of positive screening results for BDD (total DCQ score ≥ 9) was 15.8%. The prevalence of a likely diagnosis of BDD (total DCQ score of ¥ 17) was 0.83%. LIMITATIONS: The convenience sample limited the generalizability of the findings to Latin America. CONCLUSION: We encourage colleagues to be more mindful of this diagnosis and to facilitate earlier psychological evaluation in patients who are positive for BDD. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Surgical Proposition of a Slow-Growing Calvarial Exostosis in a Female Patient With a Congenital Iris Cyst of the Anterior Chamber and Mandibular Tori.

We present an unusual case of a woman in her early 50s with a slow-growing calvarial exostosis. Exostoses are bony spurs or osteomas extending outward beyond a bone's surface and may be benign or malignant. Calvarial exostoses are a less common bone tumor that can occur in the population. We present a case of a rare, slow-growing calvarial exostosis with a combination of mandibular tori and a congenital iris cyst. We discuss differentials of this exostosis and different syndromes that may cause it such as hereditary multiple exostoses and Gardner syndrome. The current article aims to spread awareness of this atypical presentation of exostoses and present our institution's surgical proposition for removing a calvarial exostosis to obtain a further histological analysis of its composition. As these masses may commonly be benign, a definitive diagnosis cannot be made through imaging alone to rule out more threatening conditions. We have addressed radiological findings and diagnostic and treatment options offered to the patient. The patient decided not to move forward with removing the mass and would continue to monitor and return should she notice any unusual or acute changes.

Human olfactory neural progenitor cells reveal differences in IL-6, IL-8, thrombospondin-1, and MCP-1 in major depression disorder and borderline personality disorder.

Background: Discovering biological markers is essential for understanding and treating mental disorders. Despite the limitations of current non-invasive methods, neural progenitor cells from the olfactory epithelium (hNPCs-OE) have been emphasized as potential biomarker sources. This study measured soluble factors in these cells in Major Depressive Disorder (MDD), Borderline Personality Disorder (BPD), and healthy controls (HC). Methods: We assessed thirty-five participants divided into MDD (n=14), BPD (n=14), and HC (n=7). MDD was assessed using the Hamilton Depression Rating Scale. BPD was evaluated using the DSM-5 criteria and the Structured Clinical Interview for Personality Disorders. We isolated hNPCs-OE, collected intracellular proteins and conditioned medium, and quantified markers and soluble factors, including Interleukin-6, interleukin-8, and others. Analysis was conducted using one-way ANOVA or Kruskal-Wallis test and linear regression. Results: We found that hNPCs-OE of MDD and BPD decreased Sox2 and laminin receptor-67 kDa levels. MASH-1 decreased in BPD, while tubulin beta-III decreased in MDD compared to controls and BPD. Also, we found significant differences in IL-6, IL-8, MCP-1, and thrombospondin-1 levels between controls and MDD, or BPD, but not between MDD and BPD. Conclusions: Altered protein markers are evident in the nhNPCs-OE in MDD and BPD patients. These cells also secrete higher concentrations of inflammatory cytokines than HC cells. The results suggest the potential utility of hNPCs-OE as an in vitro model for researching biological protein markers in psychiatric disorders. However, more extensive validation studies are needed to confirm their effectiveness and specificity in neuropsychiatric disorders.

Brachytherapy for rhabdomyosarcoma: Survey of international clinical practice and development of guidelines.

BACKGROUND AND PURPOSE: The purpose of this study was to address the lack of published data on the use of brachytherapy in pediatric rhabdomyosarcoma by describing current practice as starting point to develop consensus guidelines. MATERIALS AND METHODS: An international expert panel on the treatment of pediatric rhabdomyosarcoma comprising 24 (pediatric) radiation oncologists, brachytherapists and pediatric surgeons met for a Brachytherapy Workshop hosted by the European paediatric Soft tissue Sarcoma Study Group (EpSSG). The panel's clinical experience, the results of a previously distributed questionnaire, and a review of the literature were presented. RESULTS: The survey indicated the most common use of brachytherapy to be in combination with tumor resection, followed by brachytherapy as sole local therapy modality. HDR was increasingly deployed in pediatric practice, especially for genitourinary sites. Brachytherapy planning was mostly by 3D imaging based on CT. Recommendations for patient selection, treatment requirements, implant technique, delineation, dose prescription, dose reporting and clinical management were defined. CONCLUSIONS: Consensus guidelines for the use of brachytherapy in pediatric rhabdomyosarcoma have been developed through multicenter collaboration establishing the basis for future work. These have been adopted for the open EpSSG overarching study for children and adults with Frontline and Relapsed RhabdoMyoSarcoma (FaR-RMS).

Morin improves learning and memory in healthy adult mice.

BACKGROUND: Morin is a flavonoid found in many edible fruits. The hippocampus and entorhinal cortex play crucial roles in memory formation and consolidation. This study aimed to characterize the effect of morin on recognition and space memory in healthy C57BL/6 adult mice and explore the underlying molecular mechanism. METHODS: Morin was administered i.p. at 1, 2.5, and 5 mg/kg/24 h for 10 days. The Morris water maze (MWM), novel object recognition, novel context recognition, and tasks were conducted 1 day after the last administration. The mice's brains underwent histological characterization, and their protein expression was examined using immunohistochemistry and Western blot techniques. RESULTS: In the MWM and novel object recognition tests, mice treated with 1 mg/kg of morin exhibited a significant recognition index increase compared to the control group. Besides, they demonstrated faster memory acquisition during MWM training. Additionally, the expression of pro-brain-derived neurotrophic factor (BDNF), BDNF, and postsynaptic density protein 95 proteins in the hippocampus of treated mice showed a significant increase. In the entorhinal cortex, only the pro-BDNF increased. Morin-treated mice exhibited a significant increase in the hippocampus's number and length of dendrites. CONCLUSION: This study shows that morin improves recognition memory and spatial memory in healthy adult mice.

Predictors of malnutrition among older residents in Qatari long-term care facilities: a retrospective study.

BACKGROUND: Malnutrition is a prevalent issue among older adults in long-term care facilities and is associated with adverse health outcomes and increased healthcare costs. Identifying the predictors of malnutrition in this population is crucial for developing effective intervention strategies. This study aimed to explore the factors contributing to malnourishment among older individuals living in long-term care facilities in Qatar. METHODS: This cross-sectional study included 75 older adults from two long-term care facilities (Rumailah Hospital and Enaya Specialized Care Center) in Qatar. Baseline characteristics, including age, sex, length of stay, mortality, weight, body mass index, co-morbidities, and laboratory parameters, were assessed. Data were analyzed using the most recent version of the SPSS software, version 29. Predictors of malnutrition and mortality were identified using logistic regression analysis. RESULTS: Of the 75 older individuals included in the study, 85% (64) were malnourished. The average age of the participants was 74.89 years, with a standard deviation of 10.21. Of all participants, approximately 61% (46) were males, and 39% (29) were females. Most malnourished older adults were classified as either at "moderate (29.69%)" or "severe risk (37.50%)," according to the Geriatric Nutritional Risk Index. Malnourished participants experienced a significant percentage of weight change within 3 months (14.01 ± 7.89); the only statistically significant predictor of malnutrition was the percentage of weight change within 3 months with an odds ratio (OR) of 4.8 (confidence interval [CI] 1.56-14.75) and p-value of 0.006. Statistically significant predictors of mortality were malnutrition (OR 24.84, CI 1.09-564) and age (OR 1.07, CI 1.00-1.14). CONCLUSIONS: A significant predictor of malnutrition in older adults identified in this study was the sudden and recent change in weight, which can be employed to detect individuals at risk early and guide tailored interventions. Malnutrition is a significant predictor of mortality. Employing a multidimensional strategy to tackle malnutrition can improve outcomes for the older individuals.

Benzodiazepine Consumption, Functionality, Cognition, and Somnolence in Older Adults at a Tertiary Care Psychiatric Hospital in Mexico City.

BACKGROUND: The aging population in Mexico, particularly those aged 60 and above, faces challenges in healthcare, including potentially inappropriate prescriptions of benzodiazepines. Physiological changes in older adults make precise drug prescriptions crucial. OBJECTIVE: This study aims to evaluate and compare functionality, cognition, and daytime somnolence in older adults using benzodiazepines versus non-users. Additionally, it outlines the demographic and clinical characteristics of both groups. METHODS: A cross-sectional study enrolled 162 participants aged 60 and above, categorized as benzodiazepine consumers or non-consumers. Assessment tools included Lawton's Index, Montreal Cognitive Assessment, Epworth Sleepiness Scale, and Benzodiazepine Dependence Questionnaire. Statistical analysis employed t-tests and chi-square tests. RESULTS: Benzodiazepine users (n=81) exhibited lower cognitive scores, increased sleepiness, and reduced daily living activities compared to non-users (n=81). Demographically, BZD users had lower education levels. CONCLUSION: Benzodiazepine use in older adults is associated with cognitive decline, daytime somnolence, and functional limitations, emphasizing the need for cautious prescription practices and continual monitoring. This study contributes insights into the impact of benzodiazepines on the cognitive health of older adults in Mexico.

Circulating sex hormones in women with severe anxiety during pregnancy / Hormonas sexuales circulantes en mujeres con ansiedad severa durante el embarazo

Abstract Introduction Anxiety, mood- and stress-related behaviors are regulated by sex hormones in pregnant and non-pregnant women. Very scarce information exists about the role of sex steroids in pregnant women displaying high levels of anxiety. Objective To determine sex hormones serum levels in pregnant women exhibiting high levels of anxiety symptoms. Method The Hamilton Anxiety Rating Scale (HARS/ HAM-A) was used to assess the intensity of anxiety symptoms in third-trimester pregnant women. Two groups were included in the study, pregnant women exhibiting severe anxiety (ANX; HARS scores ≥ 25; n = 101) and healthy control subjects (CTRL; n = 40) displaying lower scores for anxiety (HARS scores ≤ 7). Estradiol (E2), progesterone (P4), and testosterone (T) serum levels were measured using a standard chemiluminescent immunoassay. Bivariate and partial correlations were performed to detect significant associations between groups, clinical measures, biochemical data, and HARS scores. Results The anxiety group (ANX) showed an increase in E2 and T serum levels (p < .001) compared to CTRL. Conversely, significantly lower P4 levels were found in the symptomatic group (p < .001) as compared to the CTRL hormone values. The P4:E2 index was significantly reduced in pregnant women with high levels of anxiety (p < .001). Negative correlations between anxiety (HARS) scores, P4 serum levels (p = .02), and P4:E2 ratio (p = .04) were found in the symptomatic group. Conversely, T serum levels displayed a positive association (p = .001) with high levels of anxiety symptoms in the same group, after adjusting our data by clinical confounders. Discussion and conclusion Serum levels of sex-steroid hormones are altered in pregnant women exhibiting severe anxiety.

Resumen Introducción La ansiedad, el estado de ánimo y el estrés están regulados por diversos esteroides sexuales. Existe poca información sobre el papel que juegan estos esteroides en mujeres embarazadas con niveles elevados de ansiedad. Objetivo Determinar los niveles séricos de hormonas sexuales en mujeres embarazadas con altos índices de síntomas de ansiedad con respecto a mujeres gestantes sanas. Método Determinación de la intensidad de síntomas ansiosos empleando la escala de Hamilton de Ansiedad (HAM-A) en 141 mujeres embarazadas en el tercer trimestre de gestación. Cuantificación de los niveles séricos de estradiol (E2), progesterona (P4) y testosterona (T) por inmunoensayo estándar. Aplicación de las correlaciones de Pearson para detectar asociaciones entre parámetros clínicos y valores hormonales entre los grupos de estudio. Resultados Las mujeres con ansiedad severa (ANX; n = 101; HAM-A ≥ 25) mostraron niveles séricos más altos de E2 y T (p < .001), así como niveles más bajos de P4 (p < .001) en relación con el grupo control (CTRL, n = 40, HAM-A < 7). Se detectó una disminución significativa en el índice P4:E2 en el grupo de ANX (p < .001) y se observaron correlaciones negativas y positivas entre los puntajes elevados de ansiedad con los niveles circulantes de P4 (p = .02), en la taza P4:E2 (p = .04) y en los niveles séricos de T (p = .001) respectivamente, al ajustar nuestros datos con variables confusoras. Discusión y conclusión Los niveles circulantes de los esteroides sexuales se encontraron alterados en mujeres con ansiedad severa.

Bibliometric analysis of peer-reviewed literature on perinatal depression in Mexico / Análisis bibliométrico de la literatura revisada por pares sobre depresión perinatal en México

Abstract Background Perinatal depression (PND) is a clinical disease developed in any stage during the pregnancy and postpartum period with serious health and economic implications. Objective The aim of this work was to analyze via bibliometrics indicators Mexico's production on PND to provide a view of the academic landscape and a comprehensive reference for subsequent research in the country. Method The Scopus and Web of Science (WoS) databases were used to perform a search for peer reviewed papers related to PND in México. The search was made following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The extracted data were processed with VOS Viewer to examine link strength and clusters associations of diverse bibliometrics variables. Results A total of 132 records were retrieved and we included 70 studies in the bibliometric analysis after application of the exclusion criteria. The authors with more papers were Navarrete L., and Asunción Lara M. The institutions with more papers were the National Institute of Perinatology, Ramón de la Fuente National Institute of Psychiatry, and National Institute of Public Health of Mexico. A diminution of the research considered in PND is observed in the last two years. Four keyword clusters were identified related to PND: symptoms, prevalence, pregnancy. Discussion and conclusion The scarce literature concerning PND in Mexico compared with other countries could be due the limited collaboration between the health institutes. An urgent need to increase research on PND in Mexico is evident to be applicable in the management of resources in the healthcare system.

Resumen Antecedentes La depresión perinatal (PND) es una enfermedad clínica que se desarrolla en cualquier etapa del embarazo y posparto con graves implicaciones sanitarias y económicas. Objetivo El objetivo de este trabajo fue analizar a través de indicadores bibliométricos la producción de México sobre PND, para brindar una visión del panorama académico y un referente integral para investigaciones posteriores en el país. Método Se utilizaron las bases de datos Scopus y Web of Science (WoS) para realizar una búsqueda de artículos revisados por pares relacionados con la PND en México. La búsqueda se realizó siguiendo los elementos de informes preferidos para revisiones sistemáticas y metaanálisis (PRISMA). Los datos extraídos se procesaron con VOS Viewer para examinar la fuerza de los enlaces y las asociaciones de grupos de diversas variables bibliométricas. Resultados Se recuperaron un total de 132 registros y se incluyeron 70 estudios en el análisis bibliométrico después de la aplicación de los criterios de exclusión. Los autores con más artículos fueron Navarrete L. y Asunción Lara M. Las instituciones con más artículos fueron el Instituto Nacional de Perinatología, el Instituto Nacional de Psiquiatría Ramón de la Fuente y el Instituto Nacional de Salud Pública de México. Se observa una disminución de las investigaciones consideradas en el PND en los últimos dos años. Se identificaron cuatro grupos de palabras clave relacionadas con la PND: síntomas, prevalencia y embarazo. Discusión y conclusión La escasa literatura sobre PND en México en comparación con otros países podría deberse a la limitada colaboración entre los institutos de salud. Se evidencia una necesidad urgente de realizar más investigaciones sobre PND en México que sean aplicables y útiles en la gestión de recursos en el sistema de salud.

Is brain perfusion correlated to switching mood states and cognitive impairment in bipolar disorder type I? A longitudinal study using perfusion imaging approach.

Type I Bipolar disorder (BD-I) is a neuropsychiatric disorder characterized by manic or mixed-featured episodes, impaired cognitive functioning, and persistent work and social functioning impairment. This study aimed to investigate within-subject; (i) differences in brain perfusion using Single-photon emission computed tomography (SPECT) between manic and euthymic states in BD-I patients; (ii) explore potential associations between altered brain perfusion and cognitive status; and (iii) examine the relationship between cerebral perfusion and mania symptom ratings. Seventeen adult patients diagnosed with BD-I in a manic episode were recruited, and clinical assessments, cognitive tests, and brain perfusion studies were conducted at baseline (mania state) and a follow-up visit 6 months later. The results showed cognitive impairment during the manic episode, which persisted during the euthymic state at follow-up. However, no significant changes in brain perfusion were observed between the manic and euthymic states. During mania, trends toward decreased perfusion in the left cerebellum and right superior parietal lobule were noted. Additionally, trends indicated a higher perfusion imbalance in the left superior and middle frontal gyrus during mania and the right superior and middle frontal gyrus during euthymia. No significant correlations existed between brain perfusion, mania symptom ratings, and cognitive performance, indicating that symptomatology might represent more than neural hemodynamics. These findings suggest that cognitive impairment may persist in BD-I patients and highlight the need for therapeutic interventions targeting cognitive deficits. More extensive studies with extended follow-up periods are warranted further to investigate brain perfusion and cognitive functioning in BD-I patients.

Factors related to academic performance in medical students / Factores relacionados con el desempeño académico en estudiantes de medicina

Abstract Introduction Academic performance in medical students can be influenced by several factors, including those related to mental health and family relationships. Objective To examine the factors affecting academic performance in medical students, specifically considering potential diagnoses of depression. Method A survey was conducted among 747 fourth-year medical students. The survey included questions on sociodemographic variables, mental health, and well-being. The Patient Health Questionnaire (PHQ) was utilized, encompassing sections on depression, anxiety, panic, eating habits, alcohol consumption, and the Stress Perception Scale. Academic performance was assessed based on students' Grade Point Average (GPA). Descriptive statistics, Pearson correlation coefficients, and a linear regression model were employed for data analysis. Results The study revealed several variables significantly associated with GPA. Age (r = -.388), financial situation (r = .241), relationships with cohabitants (r = .165), and relationships with peers (r = .217) were found to have a correlation with academic performance. Additionally, repeating a course was found to be significantly associated with a person's GPA (r = .518) even after controlling for depression. Discussion and conclusion The findings indicate that robust mental health, a favorable financial situation, and positive interpersonal relationships are crucial for achieving optimal academic performance in medical students. These results emphasize the need to address mental health concerns, promote a supportive social environment, and provide financial assistance to enhance the educational outcomes of medical students.

Resumen Introducción El desempeño académico de los estudiantes de medicina puede verse influenciado por varios factores, entre ellos los relacionados con la salud mental y las relaciones familiares. Objetivo Examinar los factores que afectan el desempeño académico en estudiantes de medicina, considerando específicamente los posibles diagnósticos de depresión. Método Se realizó una encuesta entre 747 estudiantes de cuarto año de la carrera de medicina. La encuesta incluyó preguntas sobre variables sociodemográficas, salud mental y bienestar. Se utilizó el Cuestionario de Salud del Paciente (PHQ), que comprende secciones sobre depresión, ansiedad, pánico, hábitos alimentarios, consumo de alcohol y la Escala de Percepción del Estrés. El desempeño académico se evaluó con base en el promedio de calificaciones (GPA) de los estudiantes. Se emplearon estadísticas descriptivas, coeficientes de correlación de Pearson y un modelo de regresión lineal para el análisis de datos. Resultados El estudio reveló varias variables significativamente asociadas con el GPA. Se encontró que la edad (r = -.388), la situación financiera (r = .241), las relaciones con los convivientes (r = .165) y las relaciones con los compañeros (r = .217) tenían correlación con el rendimiento académico. Además, se encontró que repetir un curso estaba significativamente asociado con el GPA de una persona (r = .518) incluso después de controlar la depresión. Discusión y conclusión Los hallazgos indican que una salud mental sólida, una situación financiera favorable y relaciones interpersonales positivas son cruciales para lograr un desempeño académico óptimo en los estudiantes de medicina. Estos resultados enfatizan la necesidad de abordar los problemas de salud mental, promover un entorno social de apoyo y brindar asistencia financiera para mejorar los resultados educativos de los estudiantes de medicina.

Value of NT-proBNP and Galectin-3 as Biomarkers in the Follow-Up of Asymptomatic Elderly Patients with Severe Aortic Stenosis.

Recognizing symptoms in elderly patients with severe aortic stenosis (AS) can be a challenge. Serum biomarkers such as Galectin-3 or N-terminal prohormone B-type natriuretic peptide (NT-proBNP) are involved in remodeling and heart failure (HF) development and could support the diagnosis of AS. We set out to test the usefulness of NT-proBNP and Galectin-3 in predicting events in this population. We designed a prospective observational case-control study, including 50 asymptomatic patients older than 70 years, diagnosed with severe degenerative AS, and 50 control individuals. The NT-proBNP and Galectin-3 levels were measured. A follow-up was carried out at 12 months to determine the occurrence of hospital admission for HF, all-cause mortality or the appearance of symptoms. The patients with severe AS had higher Galectin-3 and NT-proBNP concentrations. The area under the receiver operating characteristic curve of the NT-proBNP was 0.812 (95% CI, 0.646-0.832), and that of the Galectin-3 was 0.633 (95% CI, 0.711-0.913). NT-proBNP was a good predictor of events [HR 3.45 (95% CI 1.32-9.03), p = 0.011]. A Kaplan-Meier analysis showed that the probability of freedom from events was significant in patients who exhibited a combination of higher NT-proBNP and Galectin-3 levels (log-rank p = 0.032). Therefore, NT-proBNP was the most reliable predictor of events in asymptomatic patients with severe AS. A combination of NT-proBNP and Galectin-3 levels may be vital in the clinical follow-up of these patients and in the decision-making process.

Prevalence of transthyretin cardiac amyloidosis in elderly patients diagnosed with heart failure / Prevalencia de amiloidosis cardiaca por transtirretina en pacientes de edad avanzada con diagnóstico de insuficiencia cardiaca

Objective: There is increased interest in studying ATTR-CA, a pathology that primarily affects patients of geriatric age and is frequently underdiagnosed. We aim to establish the prevalence of ATTR-CA in a cohort of patients with a history of HFpEF and to describe its characteristics. Methods: We conducted a prospective observational study. Patients ≥75 years, clinical history of HFpEF, atrial dilation ≥34ml/m2 and left ventricular wall thickening >13mm, were included. Demographic and analytical parameters were collected, and a comprehensive geriatric assessment was performed, along with a transthoracic echocardiogram and cardiac scintigraphy. Finally, telephone follow-up was carried out at 6 and 12 months. Results: 50 patients were recruited, mean age 86±6 years, 54% women. Age and functional class (I–II vs. III–IV) were factors associated with presenting with ATTR-CA. Patients with positive scintigraphy had a median time to admission of 5.2 months (confidence interval [CI] 95% 0–10.9), while in those with negative scintigraphy, it was 12.2 months (95% CI 11.7–12.8); log-rank: p=0.064. Patients with positive scintigraphy had a median time to the combined endpoint (death and readmission) of 1.9 months (95% CI 0–6.1), and patients with negative scintigraphy of 11.9 months (95% CI 11.7–12); log-rank: p=0.027. Conclusions: ATTR-CA appears to be a prevalent etiology in elderly patients within the spectrum of HFpEF. Patients with a diagnosis of ATTR-CA had a shorter time to admission for HF and the combined event of death and admission than patients with a negative result on scintigraphy. (AU)

Objetivo: Existe un interés creciente por el estudio de AC-TTR, siendo esta una patología que afecta fundamentalmente a pacientes de edad avanzada y que es frecuentemente infradiagnosticada. Nuestro objetivo fue establecer la prevalencia de AC-TTR en una cohorte de pacientes con historia de ICFEp y describir sus características. Métodos: Estudio observacional prospectivo. Se incluyeron pacientes ≥75 años, con historia clínica de ICFEp, dilatación auricular ≥34ml/m2 y engrosamiento de la pared del ventrículo izquierdo >13mm. Se recogieron datos analíticos y demográficos, así como de la valoración geriátrica integral y se realizó un ecocardiograma transtorácico y una gammagrafía cardiaca. Finalmente se realizó seguimiento telefónico a los 6 y 12 meses. Resultados: Se incluyó a 50 pacientes, edad media 86±6 años, 54% mujeres. La edad y la clase funcional NYHA (I-II vs. III-IV) se asociaron con mayor riesgo de presentar AC-TTR. Los pacientes con gammagrafía positiva tuvieron una mediana de tiempo al ingreso de 5,2 meses (intervalo de confianza [IC] 95% 0-10,9), frente a aquellos con gammagrafía negativa que fue de 12,2 meses (IC 95% 11,7-12,8); log-rank: p=0,064. Los pacientes con gammagrafía positiva presentaron una mediana de tiempo al evento combinado (muerte y reingreso) de 1,9 meses (IC 95% 0-6,1), mientras que en aquellos con resultado negativo fue de 11,9 meses (IC 95% 11,7-12); log-rank: p=0.027. Conclusiones: La AC-TTR supone una etiología prevalente de insuficiencia cardiaca, dentro del espectro de la ICFEp, en pacientes de edad avanzada. Los individuos con diagnóstico de AC-TTR presentaron un menor tiempo al ingreso por insuficiencia cardiaca y al evento combinado de muerte y reingreso frente a aquellos pacientes con resultado negativo en la gammagrafía. (AU)

Molecular dynamics simulations depict structural motions of the whole human aryl hydrocarbon receptor influencing its binding of ligands and HSP90.

The aryl hydrocarbon receptor (AhR) has broad biological functions when its ligands activate it; the non-binding interactions with AhR have not been fully elucidated due to the absence of a complete tridimensional (3D) structure. Therefore, utilization of the whole 3D structure from Homo sapiens AhR by in silico studies will allow us to better study and analyze the binding mode of its full and partial agonists, and antagonists, as well as its interaction with the HSP90 chaperone. The 3D AhR structure was obtained from I-TASSER and subjected to molecular dynamics (MD) simulations to obtain different structural conformations and determine the most populated AhR conformer by clustering analyses. The AhR-3D structures selected from MD simulations and those from clustering analyses were used to achieve docking studies with some of its ligands and protein-protein docking with HSP90. Once the AhR-3D structure was built, its Ramachandran maps and energy showed a well-qualified 3D model. MD simulations showed that the per-Arnt-Sim homology (PAS) PAS A, PAS B, and Q domains underwent conformational changes, identifying the conformation when agonists were binding also, and HSP90 was binding near the PAS A, PAS B, and Q domains. However, when antagonists are binding, HSP90 does not bind near the PAS A, PAS B, and Q domains. These studies show that the complex agonist-AhR-HSP90 can be formed, but this complex is not formed when an antagonist is binding. Knowing the conformations when the ligands bind to AHR and the behavior of HSP90 allows for an understanding of its activity.Communicated by Ramaswamy H. Sarma.

Gaps in humanitarian WASH response: perspectives from people affected by crises, practitioners, global responders, and the literature.

Water, sanitation, and hygiene (WASH) interventions prevent and control disease in humanitarian response. To inform future funding and policy priorities, WASH 'gaps' were identified via 220 focus-group discussions with people affected by crises and WASH practitioners, 246 global survey respondents, and 614 documents. After extraction, 2,888 (48 per cent) gaps from direct feedback and 3,151 (52 per cent) from literature were categorised. People affected by crises primarily listed 'services gaps', including a need for water, sanitation, solid waste disposal, and hygiene items. Global survey respondents principally cited 'mechanism gaps' in providing services, including collaboration, WASH staffing expertise, and community engagement. Literature highlighted gaps in health (but not other) WASH intervention impacts. Overall, people affected by crises wanted the 'what' (services), responders wanted the 'how' (to supply), and researchers wanted the 'why' (health consequences). This study suggests a need for a renewed focus on basic WASH services, collaboration across stakeholders, and research on WASH outcomes beyond health.

Prevalence of transthyretin cardiac amyloidosis in elderly patients diagnosed with heart failure.

OBJECTIVE: There is increased interest in studying ATTR-CA, a pathology that primarily affects patients of geriatric age and is frequently underdiagnosed. We aim to establish the prevalence of ATTR-CA in a cohort of patients with a history of HFpEF and to describe its characteristics. METHODS: We conducted a prospective observational study. Patients ≥75 years, clinical history of HFpEF, atrial dilation ≥34ml/m2 and left ventricular wall thickening >13mm, were included. Demographic and analytical parameters were collected, and a comprehensive geriatric assessment was performed, along with a transthoracic echocardiogram and cardiac scintigraphy. Finally, telephone follow-up was carried out at 6 and 12 months. RESULTS: 50 patients were recruited, mean age 86±6 years, 54% women. Age and functional class (I-II vs. III-IV) were factors associated with presenting with ATTR-CA. Patients with positive scintigraphy had a median time to admission of 5.2 months (confidence interval [CI] 95% 0-10.9), while in those with negative scintigraphy, it was 12.2 months (95% CI 11.7-12.8); log-rank: p=0.064. Patients with positive scintigraphy had a median time to the combined endpoint (death and readmission) of 1.9 months (95% CI 0-6.1), and patients with negative scintigraphy of 11.9 months (95% CI 11.7-12); log-rank: p=0.027. CONCLUSIONS: ATTR-CA appears to be a prevalent etiology in elderly patients within the spectrum of HFpEF. Patients with a diagnosis of ATTR-CA had a shorter time to admission for HF and the combined event of death and admission than patients with a negative result on scintigraphy.

Dietary Fiber Modulates the Release of Gut Bacterial Products Preventing Cognitive Decline in an Alzheimer's Mouse Model.

Fiber intake is associated with a lower risk for Alzheimer´s disease (AD) in older adults. Intake of plant-based diets rich in soluble fiber promotes the production of short-chain fatty acids (SCFAs: butyrate, acetate, propionate) by gut bacteria. Butyrate administration has antiinflammatory actions, but propionate promotes neuroinflammation. In AD patients, gut microbiota dysbiosis is a common feature even in the prodromal stages of the disease. It is unclear whether the neuroprotective effects of fiber intake rely on gut microbiota modifications and specific actions of SCFAs in brain cells. Here, we show that restoration of the gut microbiota dysbiosis through the intake of soluble fiber resulted in lower propionate and higher butyrate production, reduced astrocyte activation and improved cognitive function in 6-month-old male APP/PS1 mice. The neuroprotective effects were lost in antibiotic-treated mice. Moreover, propionate promoted higher glycolysis and mitochondrial respiration in astrocytes, while butyrate induced a more quiescent metabolism. Therefore, fiber intake neuroprotective action depends on the modulation of butyrate/propionate production by gut bacteria. Our data further support and provide a mechanism to explain the beneficial effects of dietary interventions rich in soluble fiber to prevent dementia and AD. Fiber intake restored the concentration of propionate and butyrate by modulating the composition of gut microbiota in male transgenic (Tg) mice with Alzheimer´s disease. Gut dysbiosis was associated with intestinal damage and high propionate levels in control diet fed-Tg mice. Fiber-rich diet restored intestinal integrity and promoted the abundance of butyrate-producing bacteria. Butyrate concentration was associated with better cognitive performance in fiber-fed Tg mice. A fiber-rich diet may prevent the development of a dysbiotic microbiome and the related cognitive dysfunction in people at risk of developing Alzheimer´s disease.