Unveiling the Ro60-Ro52 complex.

The coexistence within a subcellular complex of inter-cellular proteins Ro60, responsible for preserving ncRNA quality, and Ro52, involved in intracellular proteolysis, has been a subject of ongoing debate. Employing molecular docking in tandem with experimental methods like Quartz Crystal Microbalance with Dissipation (QCM-D), Proximity Ligation Assay (PLA), and Indirect Immunofluorescence (IIF), we reveal the presence of Ro60 associating with Ro52 within the cytoplasm. This result unveils the formation of a weak transient complex with a Ka ≈ (3.7 ± 0.3) x 106 M-1, where the toroid-shaped Ro60 structure interacts with the Ro52's Fc receptor, aligning horizontally within the PRY-SPRY domains of the Ro52's homodimer. The stability of this complex relies on the interaction between Ro52 chain A and specific Ro60 residues, such as K133, W177, or L185, vital in the Ro60-YRNA bond. These findings bridge the role of Ro60 in YRNA management with Ro52's function in intracellular proteolysis, emphasizing the potential impact of transient complexes on cellular pathways. See also the graphical abstract(Fig. 1).

The child who lived: Down syndrome among Neanderthals?

Caregiving for disabled individuals among Neanderthals has been known for a long time, and there is a debate about the implications of this behavior. Some authors believe that caregiving took place between individuals able to reciprocate the favor, while others argue that caregiving was produced by a feeling of compassion related to other highly adaptive prosocial behaviors. The study of children with severe pathologies is particularly interesting, as children have a very limited possibility to reciprocate the assistance. We present the case of a Neanderthal child who suffered from a congenital pathology of the inner ear, probably debilitating, and associated with Down syndrome. This child would have required care for at least 6 years, likely necessitating other group members to assist the mother in childcare.

Next-generation sequencing reveals that miR-16-5p, miR-19a-3p, miR-451a, and miR-25-3p cargo in plasma extracellular vesicles differentiates sedentary young males from athletes.

A sedentary lifestyle and Olympic participation are contrary risk factors for global mortality and incidence of cancer and cardiovascular disease. Extracellular vesicle miRNAs have been described to respond to exercise. No molecular characterization of young male sedentary people versus athletes is available; so, our aim was to identify the extracellular vesicle miRNA profile of chronically trained young endurance and resistance male athletes compared to their sedentary counterparts. A descriptive case-control design was used with 16 sedentary young men, 16 Olympic male endurance athletes, and 16 Olympic male resistance athletes. Next-generation sequencing and RT-qPCR and external and internal validation were performed in order to analyze extracellular vesicle miRNA profiles. Endurance and resistance athletes had significant lower levels of miR-16-5p, miR-19a-3p, and miR-451a compared to sedentary people. Taking all together, exercise-trained miRNA profile in extracellular vesicles provides a differential signature of athletes irrespective of the type of exercise compared to sedentary people. Besides, miR-25-3p levels were specifically lower in endurance athletes which defines its role as a specific responder in this type of athletes. In silico analysis of this profile suggests a role in adaptive energy metabolism in this context that needs to be experimentally validated. Therefore, this study provides for the first time basal levels of circulating miRNA in extracellular vesicles emerge as relevant players in intertissue communication in response to chronic exercise exposure in young elite male athletes.

Exploring the translational landscape of the long noncoding RNA transcriptome in acute respiratory distress syndrome: it is a long way to the top.

Acute respiratory distress syndrome (ARDS) poses a significant and widespread public health challenge. Extensive research conducted in recent decades has considerably improved our understanding of the disease pathophysiology. Nevertheless, ARDS continues to rank among the leading causes of mortality in intensive care units and its management remains a formidable task, primarily due to its remarkable heterogeneity. As a consequence, the syndrome is underdiagnosed, prognostication has important gaps and selection of the appropriate therapeutic approach is laborious. In recent years, the noncoding transcriptome has emerged as a new area of attention for researchers interested in biomarker development. Numerous studies have confirmed the potential of long noncoding RNAs (lncRNAs), transcripts with little or no coding information, as noninvasive tools for diagnosis, prognosis and prediction of the therapeutic response across a broad spectrum of ailments, including respiratory conditions. This article aims to provide a comprehensive overview of lncRNAs with specific emphasis on their role as biomarkers. We review current knowledge on the circulating lncRNAs as potential markers that can be used to enhance decision making in ARDS management. Additionally, we address the primary limitations and outline the steps that will be essential for integration of the use of lncRNAs in clinical laboratories. Our ultimate objective is to provide a framework for the implementation of lncRNAs in the management of ARDS.

Cognition in Euthymic Patients with Bipolar Disorder: Do Not Forget to Account for Anxiety!

Purpose: Despite the high prevalence of anxiety disorders in BD and its known impact on cognitive performance, the presence and severity of anxious symptoms is not systematically evaluated in studies on cognition in BD. Our aim was to determine if attention and/or inhibition of cognitive interference in euthymic patients with type I Bipolar Disorder (BD-I) is affected by symptoms of anxiety. Patients and Methods: Eighty-seven euthymic BD-I patients were included. Patients with comorbidities other than Generalized Anxiety Disorder (GAD) or Panic Disorder (PD) were excluded. State anxiety was measured with the Brief Inventory of Anxious Responses and Situations (ISRA-B). Subjective cognitive performance was evaluated with the COBRA scale, attention with the Digit-Span Forward task and inhibition of cognitive interference was assessed with the StroopTest interference score. Multiple linear regression models were used to test if anxious symptoms were associated with attention or inhibition of cognitive interference, considering other known contributors for cognitive impairment. Results: Attention was unaffected by anxiety symptoms, but the overall regression for inhibition of cognitive interference was significant: years of schooling (ß=1.12, p = 0.001), cognitive complaints (ß=0.44, p = 0.008), and anxiety (ß=-0.21, p = 0.017) explained 15% of the interference score of the Stroop test (R2 = 0.15). Conclusion: Beyond residual affective symptoms, anxious symptoms seem to affect inhibition of cognitive interference. We recommend routine testing of anxiety when considering cognitive evaluations, especially when screening for cognitive deficits.

Gut microbiota signatures of vulnerability to food addiction in mice and humans.

OBJECTIVE: Food addiction is a multifactorial disorder characterised by a loss of control over food intake that may promote obesity and alter gut microbiota composition. We have investigated the potential involvement of the gut microbiota in the mechanisms underlying food addiction. DESIGN: We used the Yale Food Addiction Scale (YFAS) 2.0 criteria to classify extreme food addiction in mouse and human subpopulations to identify gut microbiota signatures associated with vulnerability to this disorder. RESULTS: Both animal and human cohorts showed important similarities in the gut microbiota signatures linked to food addiction. The signatures suggested possible non-beneficial effects of bacteria belonging to the Proteobacteria phylum and potential protective effects of Actinobacteria against the development of food addiction in both cohorts of humans and mice. A decreased relative abundance of the species Blautia wexlerae was observed in addicted humans and of Blautia genus in addicted mice. Administration of the non-digestible carbohydrates, lactulose and rhamnose, known to favour Blautia growth, led to increased relative abundance of Blautia in mice faeces in parallel with dramatic improvements in food addiction. A similar improvement was revealed after oral administration of Blautia wexlerae as a beneficial microbe. CONCLUSION: By understanding the crosstalk between this behavioural alteration and gut microbiota, these findings constitute a step forward to future treatments for food addiction and related eating disorders.

Chromosome-Y haplogroups in Asturias (Northern Spain) and their association with severe COVID-19.

The main objective of this study was to determine whether the common Y-haplogroups were be associated with the risk of developing severe COVID-19 in Spanish male. We studied 479 patients who required hospitalization due to COVID-19 and 285 population controls from the region of Asturias (northern Spain), They were genotyped for several polymorphisms that define the common European Y-haplogroups. We compared the frequencies between patients and controls aged ≤ 65 and >65 years. There were no different haplogroup frequencies between the two age groups of controls. Haplogroup R1b was less common in patients aged ≤65 years. Haplogroup I was more common in the two patient´s groups compared to controls (p = 0.02). Haplogroup R1b was significantly more frequent among hypertensive patients, without difference between the hypertensive and normotensive controls. This suggested that R1b could increase the risk for severe COVID-19 among male with pre-existing hypertension. In conclusion, we described the Y-haplogroup structure among Asturians. We found an increased risk of severe COVID-19 among haplogroup I carriers, and a significantly higher frequency of R1b among hypertensive patients. These results indicate that Y-chromosome variants could serve as markers to define the risk of developing a severe form of COVID-19.

Structure-based virtual screening of unbiased and RNA-focused libraries to identify new ligands for the HCV IRES model system.

Targeting RNA including viral RNAs with small molecules is an emerging field. The hepatitis C virus internal ribosome entry site (HCV IRES) is a potential target for translation inhibitor development to raise drug resistance mutation preparedness. Using RNA-focused and unbiased molecule libraries, a structure-based virtual screening (VS) by molecular docking and pharmacophore analysis was performed against the HCV IRES subdomain IIa. VS hits were validated by a microscale thermophoresis (MST) binding assay and a Förster resonance energy transfer (FRET) assay elucidating ligand-induced conformational changes. Ten hit molecules were identified with potencies in the high to medium micromolar range proving the suitability of structure-based virtual screenings against RNA-targets. Hit compounds from a 2-guanidino-quinazoline series, like the strongest binder, compound 8b with an EC50 of 61 µM, show low molecular weight, moderate lipophilicity and reduced basicity compared to previously reported IRES ligands. Therefore, it can be considered as a potential starting point for further optimization by chemical derivatization.

Nursing students' experience of approaching risk for suicide behaviour through simulated environments: A content analysis study.

BACKGROUND: Suicide is a major public health problem, especially among the young population. Nurses are in a unique position to prevent it due to their constant contact with patients. However, addressing suicidal behaviour can be complicated by the emotional responses it elicits. Simulation has been shown to be an effective tool to increase the self-confidence of nursing students in dealing with these sensitive situations in a safe environment prior to dealing with real patients. AIM: To explore nursing students' perceptions, thoughts, and emotions about their performance in dealing with risk for suicidal behaviour through simulated scenarios. DESIGN: Qualitative descriptive study. METHODS: Students of Mental Health and Psychiatric II in the third year of the Nursing course at the University of Málaga were invited to explain their experience by answering a questionnaire of three open-ended questions following their participation in the simulated scenarios of the course. RESULTS: A total of 72 students participated. Content analysis of the written responses identified three main themes: (i) Emotions experienced during the simulation; (ii) Self-criticism of the performance/intervention; (iii) Student evaluation of the learning experience. Most of the students indicated at some point during the clinical scenario, they had felt anxiety, proposing possible improvements in their own performance. The clinical scenario that elicited the most negative emotions was that of a person diagnosed with borderline personality disorder. CONCLUSION: Clinical simulations contribute to a better understanding of nursing practice with mental health patients and the need for training in emotional and therapeutic communication skills among students.

Evaluating Pigments as a Biosignature: Abiotic/Prebiotic Synthesis of Pigments and Pigment Mimics in Planetary Environments.

Pigments serve a multitude of functions in biology including light harvesting for photosynthesis, radiation protection, membrane support, and defense. The ubiquity of pigments-especially within extremophiles found in high-radiation, high-salinity, and dry environments-and their detectability via mission-ready techniques have elevated these molecules as promising targets in the search for evidence of life elsewhere. Moreover, the detection of pigments has been proposed as a "smoking gun" for extraterrestrial life as it has been suggested that these molecules cannot be generated abiotically. However, while pigments may hold promise as a biosignature, current understanding of their possible prebiotic origins remains understudied and uncertain. Better understanding of the abiotic synthesis of pigments is critical for evaluating the biogenicity of any pigment detected during missions, including by the Mars Perseverance rover or from returned samples. Compounding this uncertainty is the broad definition of pigment as it includes any compound capable of absorbing visible light and by itself does not specify a particular chemical motif. While not experimentally verified, there are promising prebiotic routes for generating pigments including hemes, chlorophylls, and carotenoids. Herein, we review the biochemistry of pigments, the inherent assumptions made when searching for these molecules in the field, their abiotic synthesis in industry and prebiotic reactions, prebiotically relevant molecules that can mimic their spectral signatures, and implications/recommendations for future work.

Amiodarone triggered Kounis syndrome complicated by refractory cardiac arrest rescued with VA-ECMO.

Key Clinical Message: An interesting case that shows an infrequent cause of cardiorespiratory arrest such as coronary vasospasm due to intravenous amiodarone induced Kounis syndrome. It highlights the usefulness of circulatory support with ECMO in the scenario of CPR. Abstract: A patient with atrial fibrillation was admitted for an elective electrical cardioversion. He was given an amiodarone bolus that triggered Kounis syndrome with cardiac arrest due to vasospasm requiring emergency coronary angiography with infusion of nitroglycerin. Due to following refractory shock and severe refractory hypoxemia required mechanical circulatory support with ECMO and inhaled nitric oxide with favorable evolution. Allergy to amiodarone was later confirmed.

A Paradigm Shift on Deinstitutionalization and Dementia Care: A Narrative Review.

This narrative explores the impact of deinstitutionalization policies on the quality of life and care outcomes for individuals with Alzheimer's disease and related dementias. We offer a historical perspective on these policies, their implications on dementia care, and the barriers to deinstitutionalization. The potential benefits of deinstitutionalization, such as improved quality of life and access to community-based support and services, are highlighted. Challenges and controversies surrounding safety, caregiver burden, and resource allocation are also examined. Ethical considerations related to the autonomy and decision-making capacity of people living with dementia are discussed. We present best practices and innovative models in dementia care that balance deinstitutionalization with appropriate care. We further put forth recommendations for future research and policy development in dementia care and deinstitutionalization, emphasizing the need for a balanced approach that respects the autonomy and preferences of people living with dementia while ensuring their safety and well-being.

Psychometric Properties of the Spanish Version of the Cognitive Problems and Strategies Assessment in Patients with Bipolar Disorder.

Cognitive deficits play an important role in Bipolar Disorder (BPD). The Cognitive Problems and Strategies Assessment (CPSA) is a measure that evaluates the patient's perception of cognitive difficulties, and the spontaneous use of compensatory strategies and could thus have potential utility for clinical practice in patients with BPD. Our aim was to determine the validity and reliability of the Cognitive Problems and Strategies Assessment (CPSA) in Bipolar Disorder (BPD). Ninety-three BPD outpatients and 90 controls completed the Assessment of Problems with Thinking and Memory (APTM) questionnaire and the Assessment of Memory and Thinking Strategies (AMTS) questionnaire which constitute the CPSA, the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA), as a measure of convergent validity, and general sociodemographic data. Cronbach's alpha coefficient, Spearman's correlation coefficient and independent sample t tests were used for Internal consistency, Convergent validity and Discriminant validity. The APTM had a Cronbach's alpha coefficient of 0.93 and the AMTS 0.90. The COBRA score and the APTM were significantly correlated. BPD patients exhibited higher scores on the APTM and lower scores on the AMTS than controls. The present instrument enriches the clinician's repertoire for rapid and inexpensive cognitive evaluation in BPD.

Healthcare service use for children with chronic complex diseases: A longitudinal six-year follow-up study.

PURPOSE: The objective was analysed the patterns use of healthcare services of this population and the influence of their clinical and sociodemographic characteristics. DESIGN AND METHODS: A six-year longitudinal follow-up study was performed to evaluate the annual healthcare resources use and clinical data among children with complex chronic diseases in Spain between 2015 and 2021. The sample trends in healthcare usage and the associated factors were analysed using ANCOVA and multivariable linear regression models. RESULTS: Patients had high attendance during the follow-up period, with >15 episodes year. This trend decreased over time, especially in children with oncological diseases compared with other diseases (F (16.75; 825.4) = 32.457; p < 0.001). A multivariable model showed that children with a greater number of comorbidities (ß = 0.17), shorter survival time (ß = -0.23), who had contact with the palliative care unit (ß = 0.16), and whose mothers had a higher professional occupation (ß = 0.14), had a greater use of the healthcare system. CONCLUSIONS: Children with a higher number of comorbidities and the use of medical devices made a greater frequentation of health services, showing a trend of decreasing use over time. Socioeconomic factors such as mothers' occupational status determine healthcare frequentation. These results suggest the existence of persistent gaps in care coordination sustained over time. PRACTICAL IMPLICATIONS: Systematized and coordinated models of care for this population should consider the presence of inequalities in health care use.

Epidemiología quirúrgica de la obstrucción intestinal por adherencias en el servicio de cirugía general del Complejo Hospitalario Dr. Arnulfo Arias Madrid. 2015-2020, Panamá

Introducción: La obstrucción intestinal supone un 20% de las consultas por dolor abdominal en urgencias y hasta un 75% se deben a adherencias por cirugías previas. A pesar de las altas tasas de resolución con el tratamiento conservador, es a menudo recurrente y amerita manejo quirúrgico. Objetivo: Determinar la epidemiología quirúrgica de la obstrucción intestinal por adherencias en el servicio de cirugía general del Complejo Hospitalario Dr. Arnulfo Arias Madrid en el período 2015-2020. Metodología: Se realizó un estudio observacional descriptivo, retrospectivo, transversal mediante revisión de expedientes de pacientes con diagnóstico de obstrucción intestinal por adherencias. Resultados: El 54% de los pacientes fueron mujeres y el 46% hombres. Con mayor frecuencia en >65 años y una edad media de 72,5 años. La mayoría de los pacientes presentaban al menos un antecedente quirúrgico abdominal previo (89%). El tiempo transcurrido desde la última cirugía fue más de 10 años (53%). La respuesta al tratamiento conservador fue del 75%. De los pacientes operados, al 77% se le realizó adherenciolisis, al 13% resección y anastomosis intestinal, al 3% ostomías y al 7% otros procedimientos. La moda del tiempo de hospitalización fue de <5 días para el manejo conservador y de 5-10 días para el manejo quirúrgico. Conclusiones: Este estudio marca el inicio de una serie de proyectos, encaminados a evaluar los riesgos y resultados del tratamiento, y decidir el momento óptimo para la intervención quirúrgica, con el objetivo primordial de disminuir la morbi-mortalidad y mejorar la calidad de vida de la población. (provisto por Infomedic International)

Introduction: Intestinal obstruction accounts for 20% of emergency department visits for abdominal pain and up to 75% are due to adhesions from previous surgery. Despite high resolution rates with conservative treatment, it is often recurrent and requires surgical management. Objective: To determine the surgical epidemiology of intestinal obstruction due to adhesions in the general surgery service of the Complejo Hospitalario Dr. Arnulfo Arias Madrid in the period 2015-2020. Methodology: A descriptive, retrospective, cross-sectional, retrospective, observational study was carried out by reviewing the records of patients with a diagnosis of intestinal obstruction due to adhesions. Results: 54% of the patients were women and 46% men. With a higher frequency in >65 years and a mean age of 72.5 years. Most patients had at least one previous abdominal surgical history (89%). The time elapsed since the last surgery was more than 10 years (53%). The response to conservative treatment was 75%. Of the operated patients, 77% underwent adhesiolysis, 13% underwent intestinal resection and anastomosis, 3% underwent ostomies and 7% underwent other procedures. The mode of hospitalization time was <5 days for conservative management and 5-10 days for surgical management. Conclusions: This study marks the beginning of a series of projects, aimed at evaluating the risks and results of treatment, and deciding the optimal time for surgical intervention, with the primary objective of decreasing morbi-mortality and improving the quality of life of the population. (provided by Infomedic International)

Immunoglobulin genes and severity of COVID-19.

There is tremendous interindividual and interracial variability in the outcome of SARS-CoV-2 infection, suggesting the involvement of host genetic factors. Here, we investigated whether IgG allotypes GM (γ marker) 3 and GM 17, genetic markers of IgG1, contributed to the severity of COVID-19. IgG1 plays a pivotal role in response against SARS-CoV-2 infection. We also investigated whether these GM alleles synergistically/epistatically with IGHG3 and FCGR2A alleles-which have been previously implicated in COVID-19-modulated the extent of COVID-19 severity. The study population consisted of 316 COVID-19 patients who needed treatment in the intensive care unit of Hospital Universitario Central de Asturias. All individuals were genotyped for GM 3/17, IGHG3 hinge length, and FCGR2A rs1801274 A/G polymorphisms. Among the 316 critical patients, there were 86 deaths. The risk of death among critical patients was significantly higher in subjects with GM 17 (IgG1) and short hinge length (IgG3). GM 17-carriers were at almost three-fold higher risk of death than non-carriers (p < 0.001; OR = 2.86, CI 1.58-5.16). Subjects with short hinge length of IgG3 had a two-fold higher risk of death than those with medium hinge length (p = 0.01; OR = 2.16, CI 1.19-3.90). GM 3/3 and IGHG3 (MM) genotypes were less frequent among death vs. survivors (9% vs 36%, p < 0.001) and associated with protective effect (OR = 0.18, 95% CI = 0.08-0.39). This is the first report implicating IgG1 allotypes in COVID-19-spurred death. It needs to be replicated in an independent study population.

The great imitator: Tuberculosis with lymphadenopathy and splenomegaly.

Tuberculosis (TB) is a leading infectious killer worldwide. Over two-thirds of new TB diagnoses in the United States occur among first-generation immigrants, especially within a year of migration. Hodgkin lymphoma (HL) accounts for a minority of lymphoma cases but presents similarly to disseminated or extrapulmonary TB. Clinical overlap between TB and HL increases patient risk of misdiagnosis. Concomitant presentation of both diseases is not uncommon but infrequently reported. We present a case of isoniazid-resistant TB with progressively worsening lymphadenopathy and splenomegaly despite appropriate TB treatment. The patient was diagnosed with HL following PET/CT and axillary lymph node biopsy.

Appendicular Muscle Mass Index as the Most Important Determinant of Bone Mineral Content and Density in Small for Gestational Age Children.

Preterm small for gestational age (SGA) children are at increased risk for low bone mineral content later in life; however, data on SGA children born at term are scarce. We included 44 SGA and 57 adequate for gestational age (AGA) children aged 6 to 11 years to compare bone mineral density (BMD) and bone mineral content (BMC) and to identify which anthropometric and biochemical values influence bone mineralization in these children. Fat mass, appendicular skeletal muscle mass index (ASMMI), BMC, and BMD were significantly lower in SGA children than in AGA (P ≤ .005). Appendicular muscle mass index correlated with BMC(TBLH,FN,L1-L4) and BMD(TBLH,FN,L1-L4) in both groups (r2 = 0.7, P < .05). In multivariate analysis, ASMMI was strongly associated with BMC and BMD in both groups. There were no differences in clinical biomarkers, calcium intake, and physical activity between the groups. Achieving adequate muscle mass contributes to adequate bone mineralization and a lower risk for low BMC and BMD in SGA children.

Cardiovascular event in a cohort of rheumatoid arthritis patients in Castilla-La Mancha: Utility of carotid ultrasound.

Rheumatoid Arthritis (RA) has a mortality rate 1,3 to 3 times higher than the general population, with cardiovascular mortality accounting for 40-50% of cases. Currently, cardiovascular disease is considered an extraarticular manifestation of RA (OR: 1,5-4,0). Ultrasound measurement of the intima-media thickness (IMT) of the common carotid artery and the presence of atherosclerotic plaques (AP) is a non-invasive method and a surrogate marker of subclinical arteriosclerosis. OBJECTIVE: To determine if subclinical arteriosclerosis findings through carotid ultrasound can serve as a good predictor of cardiovascular events (CVE) development in a cohort of RA patients over a 10-year period. METHODOLOGY: A cohort of RA patients seen in the Rheumatology outpatient clinic of a hospital in Castilla La Mancha in 2013 was evaluated. A prospective evaluation for the development of CVE over the following 10 years was conducted, and its correlation with previous ultrasound findings of IMT and AP was analyzed. RESULTS: Eight (24%) patients experienced a CVE. Three (9%) had heart failure, three (9%) had a stroke, and two (6%) experienced acute myocardial infarction. RA patients who developed a CVE had a higher IMT (0,97 +/- 0.08 mm) compared to the RA patients without CV complications (0,74 +/- 0.15 mm) (p = 0,003). The presence of IMT ≥ 0.9 mm and AP had a relative risk of 12,25 (p = 0,012) and 18,66 (p = 0,003), respectively, for the development of a CVE. CONCLUSIONS: Carotid ultrasound in RA patients may allow for early detection of subclinical atherosclerosis before the development of CVE, with IMT ≥ 0.9 mm being the most closely associated finding with CVE, unaffected by age.