Homeostasis of cytoplasmic crowding by cell wall fluidization and ribosomal counterions.

In bacteria, algae, fungi, and plant cells, the wall must expand in concert with cytoplasmic biomass production, otherwise cells would experience toxic molecular crowding1,2 or lyse. But how cells achieve expansion of this complex biomaterial in coordination with biosynthesis of macromolecules in the cytoplasm remains unexplained3, although recent works have revealed that these processes are indeed coupled4,5. Here, we report a striking increase of turgor pressure with growth rate in E. coli, suggesting that the speed of cell wall expansion is controlled via turgor. Remarkably, despite this increase in turgor pressure, cellular biomass density remains constant across a wide range of growth rates. By contrast, perturbations of turgor pressure that deviate from this scaling directly alter biomass density. A mathematical model based on cell wall fluidization by cell wall endopeptidases not only explains these apparently confounding observations but makes surprising quantitative predictions that we validated experimentally. The picture that emerges is that turgor pressure is directly controlled via counterions of ribosomal RNA. Elegantly, the coupling between rRNA and turgor pressure simultaneously coordinates cell wall expansion across a wide range of growth rates and exerts homeostatic feedback control on biomass density. This mechanism may regulate cell wall biosynthesis from microbes to plants and has important implications for the mechanism of action of antibiotics6.

Temporal Trends, Outcomes, and Predictors of Next-Day Discharge and Readmission Following Uncomplicated Evolut Transcatheter Aortic Valve Replacement: A Propensity Score-Matched Analysis.

BACKGROUND: Next-day discharge (NDD) outcomes following uncomplicated self-expanding transcatheter aortic valve replacement have not been studied. Here, we compare readmission rates and clinical outcomes in NDD versus non-NDD transcatheter aortic valve replacement with Evolut. METHODS AND RESULTS: Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry patients (n=29 597) undergoing elective transcatheter aortic valve replacement with self-expanding supra-annular valves (Evolut R, PRO, and PRO+) from July 2019 to June 2021 were stratified by postprocedure length of stay: ≤1 day (NDD) versus >1 day (non-NDD). Propensity score matching was used to compare risk adjusted 30-day readmission rates and 1-year outcomes in NDD versus non-NDD, and multivariable regression to determine predictors of NDD and readmission. Between the first and last calendar quarter, the rate of NDD increased from 45.4% to 62.1% and median length of stay decreased from 2 days to 1. Propensity score matching produced relatively well-matched NDD and non-NDD cohorts (n=10 549 each). After matching, NDD was associated with lower 30-day readmission rates (6.3% versus 8.4%; P<0.001) and 1-year adverse outcomes (death, 7.0% versus 9.3%; life threatening/major bleeding, 1.6% versus 3.4%; new permanent pacemaker implantation/implantable cardioverter-defibrillator, 3.6 versus 11.0%; [all P<0.001]). Predictors of NDD included non-Hispanic ethnicity, preexisting permanent pacemaker implantation/implantable cardioverter-defibrillator, and previous surgical aortic valve replacement. CONCLUSIONS: Most patients undergoing uncomplicated self-expanding Evolut transcatheter aortic valve replacement are discharged the next day. This study found that NDD can be predicted from baseline patient characteristics and was associated with favorable 30-day and 1-year outcomes, including low rates of permanent pacemaker implantation and readmission.

Development and validation of a Spanish version of the Obstetric Quality of Recovery-10 item score (ObsQoR-10-Spanish).

Background: Spanish is the second most spoken language globally with around 475 million native speakers. We aimed to validate a Spanish version of the Obstetric Quality of Recovery-10 item (ObsQoR-10) patient-reported outcome measure. Methods: ObsQoR-10-Spanish was developed using EuroQoL methodology. ObsQoR-10-Spanish was assessed in 100 Spanish-speaking patients undergoing elective Caesarean or vaginal delivery. Patients <38 weeks, undergoing an intrapartum Caesarean delivery, intrauterine death, or maternal admission to the intensive care unit (ICU) were excluded. Validity was assessed by evaluating (i) convergent validity-correlation with 24-h EuroQoL and global health visual analogue scale (GHVAS) scores (0-100); (ii) discriminant validity-difference in ObsQoR-10-Spanish score for patients with GHVAS scores >70 vs <70; (iii) hypothesis testing-correlation of ObsQoR score with maternal and neonatal factors; and (iv) cross-cultural validity assessed using differential item functioning analysis. Reliability was assessed by evaluating: (i) internal consistency; (ii) split-half reliability and (iii) test-retest reliability; and (iv) floor and ceiling effects. Results: One hundred patients were approached, recruited, and completed surveys. Validity: (i) convergent validity: the ObsQoR 24-h score correlated moderately with the 24-h EuroQoL (r=-0.632) and GHVAS scores (r=0.590); (ii) discriminant validity: the ObsQoR-10-Spanish 24-h scores were higher in women who delivered vaginally compared to via Caesarean delivery, (mean [standard deviation] scores were 89 [9] vs 81 [12]; P<0.001). The 24-h ObsQoR-Spanish scores were lower in patients experiencing a poor vs a good recovery (mean [standard deviation] scores were 76 [12.3] vs 87.1 [10.6]; P=0.001); (iii) hypothesis testing: the ObsQoR-10 score correlated negatively with age (r=-0.207) and positively with 5-min (r=0.204) and 10-min (r=0.243) Apgar scores. Remaining correlations were not significant; and (iv) differential item functioning analysis suggested no potential bias among the 10 items. Reliability: (i) internal consistency was good (Cronbach alpha=0.763); (ii) split-half reliability was good (Spearman-Brown prophesy reliability estimate of 0.866); (iii) test-retest reliability was excellent with an intra-class correlation coefficient of 0.90; and (iv) floor and ceiling effects: six patients scored a maximum total ObsQoR-10 score. Conclusions: The ObsQoR-10-Spanish patient-reported outcome measure is valid, reliable, and clinically feasible, and should be considered for use in Spanish-speaking women to assess quality of inpatient postpartum recovery.

Brain and cognitive changes in patients with long COVID compared with infection-recovered control subjects.

Between 2.5 and 28% of people infected with SARS-CoV-2 suffer Long COVID or persistence of symptoms for months after acute illness. Many symptoms are neurological, but the brain changes underlying the neuropsychological impairments remain unclear. This study aimed to provide a detailed description of the cognitive profile, the pattern of brain alterations in Long COVID and the potential association between them. To address these objectives, 83 patients with persistent neurological symptoms after COVID-19 were recruited, and 22 now healthy controls chosen because they had suffered COVID-19 but did not experience persistent neurological symptoms. Patients and controls were matched for age, sex and educational level. All participants were assessed by clinical interview, comprehensive standardized neuropsychological tests and structural MRI. The mean global cognitive function of patients with Long COVID assessed by ACE III screening test (Overall Cognitive level - OCLz= -0.39± 0.12) was significantly below the infection recovered-controls (OCLz= +0.32± 0.16, p< 0.01). We observed that 48% of patients with Long COVID had episodic memory deficit, with 27% also impaired overall cognitive function, especially attention, working memory, processing speed and verbal fluency. The MRI examination included grey matter morphometry and whole brain structural connectivity analysis. Compared to infection recovered controls, patients had thinner cortex in a specific cluster centred on the left posterior superior temporal gyrus. In addition, lower fractional anisotropy (FA) and higher radial diffusivity (RD) were observed in widespread areas of the patients' cerebral white matter relative to these controls. Correlations between cognitive status and brain abnormalities revealed a relationship between altered connectivity of white matter regions and impairments of episodic memory, overall cognitive function, attention and verbal fluency. This study shows that patients with neurological Long COVID suffer brain changes, especially in several white matter areas, and these are associated with impairments of specific cognitive functions.

Impacts of attacks to female health care workers in three territories of Colombia.

BACKGROUND: This study explores the impacts of attacks perpetrated in the context of armed conflict, to female health workers in three Colombian territories. METHODS: We conducted a document review of the reports and databases of the Colombian Truth Commission, 17 in-depth semi-structured interviews with experts on the national and regional armed conflict and the medical mission, and 26 female health workers who were victims of attacks. RESULTS: Experts and female health workers reported attacks to health activities, facilities, equipment, and personnel, including attacks to traditional doctors belonging to indigenous communities. The most frequent attacks were threats and retention of health personnel; theft of supplies and medicines; damage and use of infrastructure and means of transport for purposes other than health care; and hinderance of health service provision. The attacks occurred in a framework of structural violence that intersects with poverty, racism, and gender bias. The impacts of these attacks include gender-based violence, significant disruption of the lives of health workers, and physical, emotional, psychological, social, and economic effects on the victims and their families. The government response to protect victims and populations has been absent or insufficient. CONCLUSIONS: Attacks to health care were reported in all the studied territories obstructing adequate health care. Impacts of these attacks affect negatively the professional and personal life of the workers and are aggravated by structural violence and absent or little institutional response.

Swissped-RECOVERY: masked independent adjudication for the interpretation of non-randomised treatment in a two-arm open-label randomised controlled trial (methylprednisolone vs immunoglobulins) in Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) involving 10 secondary and tertiary paediatric hospitals in Switzerland.

OBJECTIVES: In trials of acute severe infections or inflammations frequent administration of non-randomised treatment (ie, intercurrent event) in response to clinical events is expected. These events may affect the interpretation of trial findings. Swissped-RECOVERY was set up as one of the first randomised controlled trials worldwide, investigating the comparative effectiveness of anti-inflammatory treatment with intravenous methylprednisolone or intravenous immunoglobulins in children and adolescents with Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). We present one approach towards improving the interpretation of non-randomised treatment in a randomised controlled trial. DESIGN: This is a pre-planned ancillary analysis of the Swissped-RECOVERY trial, a randomised multicentre open-label two-arm trial. SETTING: 10 Swiss paediatric hospitals (secondary and tertiary care) participated. PARTICIPANTS: Paediatric patients hospitalised with PIMS-TS. INTERVENTIONS: All patient-first intercurrent events, if applicable, were presented to an independent adjudication committee consisting of four international paediatric COVID-19 experts to provide independent clinical adjudication to a set of standardised questions relating to whether additional non-randomised treatments were clinically indicated and disease classification at the time of the intercurrent event. RESULTS: Of 41 treatments in 75 participants (24/41 (59%) and 17/41 (41%) in the intravenous methylprednisolone and immunoglobulin arms of the trial, respectively), two-thirds were considered indicated. The most common treatment (oral glucocorticoids, 14/41, 35%) was mostly considered not indicated (11/14, 79%), although in line with local guidelines. Intercurrent events among patients with Shock-like PIMS-TS at baseline were mostly considered indicated. A significant proportion of patients with undifferentiated PIMS-TS at baseline were not attributed to the same group at the time of the intercurrent event (6/12 unchanged, 4/12 Kawasaki disease-like, 2/12 Shock-like). CONCLUSION: The masked adjudication of intercurrent events contributes to the interpretation of results in open-label trials and should be incorporated in the future. TRIAL REGISTRATION NUMBERS: SNCTP000004720 and NCT04826588.

Electronic Tongues and Noses: A General Overview.

As technology advances, electronic tongues and noses are becoming increasingly important in various industries. These devices can accurately detect and identify different substances and gases based on their chemical composition. This can be incredibly useful in fields such as environmental monitoring and industrial food applications, where the quality and safety of products or ecosystems should be ensured through a precise analysis. Traditionally, this task is performed by an expert panel or by using laboratory tests but sometimes becomes a bottleneck because of time and other human factors that can be solved with technologies such as the provided by electronic tongue and nose devices. Additionally, these devices can be used in medical diagnosis, quality monitoring, and even in the automotive industry to detect gas leaks. The possibilities are endless, and as these technologies continue to improve, they will undoubtedly play an increasingly important role in improving our lives and ensuring our safety. Because of the multiple applications and developments in this field in the last years, this work will present an overview of the electronic tongues and noses from the point of view of the approaches developed and the methodologies used in the data analysis and steps to this aim. In the same manner, this work shows some of the applications that can be found in the use of these devices and ends with some conclusions about the current state of these technologies.

Clinical practice guidelines for diagnostic and treatment of the chronic heart failure.

Chronic heart failure continues to be one of the main causes of impairment in the functioning and quality of life of people who suffer from it, as well as one of the main causes of mortality in our country and around the world. Mexico has a high prevalence of risk factors for developing heart failure, such as high blood pressure, diabetes, and obesity, which makes it essential to have an evidence-based document that provides recommendations to health professionals involved in the diagnosis and treatment of these patients. This document establishes the clinical practice guide (CPG) prepared at the initiative of the Mexican Society of Cardiology (SMC) in collaboration with the Iberic American Agency for the Development and Evaluation of Health Technologies, with the purpose of establishing recommendations based on the best available evidence and agreed upon by an interdisciplinary group of experts. This document complies with international quality standards, such as those described by the US Institute of Medicine (IOM), the National Institute of Clinical Excellence (NICE), the Intercollegiate Network for Scottish Guideline Development (SIGN) and the Guidelines International Network (G-I-N). The Guideline Development Group was integrated in a multi-collaborative and interdisciplinary manner with the support of methodologists with experience in systematic literature reviews and the development of CPG. A modified Delphi panel methodology was developed and conducted to achieve an adequate level of consensus in each of the recommendations contained in this CPG. We hope that this document contributes to better clinical decision making and becomes a reference point for clinicians who manage patients with chronic heart failure in all their clinical stages and in this way, we improve the quality of clinical care, improve their quality of life and reducing its complications.

La insuficiencia cardiaca crónica sigue siendo unas de las principales causas de afectación en el funcionamiento y en la calidad de vida de las personas que la presentan, así como una de las primeras causas de mortalidad en nuestro país y en todo el mundo. México tiene una alta prevalencia de factores de riesgo para desarrollar insuficiencia cardiaca, tales como hipertensión arterial, diabetes y obesidad, lo que hace imprescindible contar con un documento basado en la evidencia que brinde recomendaciones a los profesionales de la salud involucrados en el diagnóstico y el tratamiento de estos pacientes. Este documento establece la guía de práctica clínica (GPC) elaborada por iniciativa de la Sociedad Mexicana de Cardiología (SMC) en colaboración con la Agencia Iberoamericana de Desarrollo y Evaluación de Tecnologías en Salud, con la finalidad de establecer recomendaciones basadas en la mejor evidencia disponible y consensuadas por un grupo interdisciplinario y multicolaborativo de expertos. Cumple con estándares internacionales de calidad, como los descritos por el Institute of Medicine de los Estados Unidos de América (IOM), el National Institute of Clinical Excellence (NICE) del Reino Unido, la Intercollegiate Network for Scottish Guideline Development (SIGN) de Escocia y la Guidelines International Network (G-I-N). El grupo de desarrollo de la guía se integró de manera interdisciplinaria con el apoyo de metodólogos con experiencia en revisiones sistemáticas de la literatura y en el desarrollo de GPC. Se llevó a cabo y se condujo metodología de panel Delphi modificado para lograr un nivel de consenso adecuado en cada una de las recomendaciones contenidas en esta GPC. Esperamos que este documento contribuya para la mejor toma de decisiones clínicas y se convierta en un punto de referencia para los clínicos que manejan pacientes con insuficiencia cardiaca crónica en todas sus etapas clínicas, y de esta manera logremos mejorar la calidad en la atención clínica, aumentar la calidad de vida de los pacientes y disminuir las complicaciones de la enfermedad.

Detection of intrathecal IgG antibody for varicella and measles diagnosis by evaluation and comparison of a commercial IgG chemiluminescent immunoassay with two ELISAs.

OBJECTIVES: Analyse alternative methods of intrathecal antibody detection by comparing chemiluminescent immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) techniques to determine if CLIA can replace ELISA in the diagnosis of CNS infections. METHODS: A panel of 280 paired samples-cerebrospinal fluid (CSF) and serum-with known antibody reactivities (Varicella, n = 60; Measles, n = 120) and negative samples (n = 100) were used to evaluate the performance of six serological test kits (Enzygnost, VirClia®, and Serion ELISA (Measles and Variella). RESULTS: For Measles virus IgG, the VirClia® IgG monotest revealed 97% and 94% positive and negative agreement to the Enzygnost as reference test, respectively. In contrast, Serion ELISA kits yielded values of 18% and 90%. For the Varicella Zoster virus (VZV) IgG, the VirClia® IgG monotest showed 97% and 90% positive and negative agreement compared to Enzygnost. The Serion ELISA kits showed values of 55% and 86%, respectively. ROC analysis revealed that the areas under the curve for Measles and VZV IgGs were 0.7 and 0.852, respectively, using the Serion kit, and 0.963 and 0.955, for Vircell S.L CLIA technique. VirClia® monotest values were calculated using an antibody index cut-off of 1.3. CONCLUSION: The findings indicate that CLIA testing can improve antibody detection in CSF samples, aiding the diagnosis of infectious neurological impairments.

Exposure to green spaces, cardiovascular risk biomarkers and incident cardiovascular disease in older adults: The Seniors-Enrica II cohort.

INTRODUCTION: The impact of residential green spaces on cardiovascular health in older adults remains uncertain. METHODS: Cohort study involving 2114 adults aged ≥ 65 years without cardiovascular disease (CVD), residing in five dense municipalities (Prince et al., 2015) of the Madrid region and with detailed characterization of their socioeconomic background, health behaviors, CVD biological risk factors, and mental, physical, and cognitive health. Greenness exposure was measured using the Normalized Difference Vegetation Index (NDVI) at varying distances from participants' homes. Traffic exposure, neighborhood environment, neighborhood walkability, and socioeconomic deprivation at the census level were also assessed. Serum N-terminal pro-B-type natriuretic peptide (NT-ProBNP), high-sensitivity troponin T (hs-TnT), interleukin 6 (IL-6), and Growth Differentiation Factor 15 (GDF-15) were measured at baseline, and incident CVD events identified through electronic medical records (International Classification of Primary Care-2 codes K74, K75, K77, K90, and K92). RESULTS: After adjusting for sex, age, educational attainment, financial hardship and socioeconomic deprivation at the census level, an interquartile range (IQR) increase in NDVI at 250, 500, 750, and 1000 m around participants' homes was associated with mean differences in ProBNP of -5.56 % (95 %CI: -9.77; -1.35), -5.05 % (-9.58; -0.53), -4.24 % (-8.19, -0.19), and -4.16 % (-7.59; -0.74), respectively; and mean differences in hs-TnT among diabetic participants of -8.03 % (95 %CI: -13.30; -2.77), -9.52 % (-16.08; -2.96), -8.05 % (-13.94, -2.16) and -5.56 % (-10.75; -0.54), respectively. Of similar magnitude, although only statistically significant at 250 and 500 m, were the observed lower IL-6 levels with increasing greenness. GDF-15 levels were independent of NDVI. In prospective analyses (median follow-up 6.29 years), an IQR increase in residential greenness at 500, 750, and 1000 m was associated with a lower risk of incident CVD. The variables that contributed most to the apparent beneficial effects of greenness on CVD were lower exposure to traffic, improved cardiovascular risk factors, and enhanced physical performance. Additionally, neighborhood walkability and increased physical activity were notable contributors among individuals with diabetes. CONCLUSION: Increased exposure to residential green space was associated with a moderate reduction in CVD risk in older adults residing in densely populated areas.

Segmental Clavicle Fracture in a Polytraumatized Patient: Case Report.

Clavicle fracture represents 5% of the fractures in adults. However, segmental clavicle fractures are infrequent and have been understudied in the current literature. Cases have been reported showing adequate results with both surgical and conservative management, and yet, it has not been possible to reach a consensus regarding diagnosis or management of such condition. A patient with a middle and lateral segmental clavicle fracture is reported, after presenting multiple trauma in a road traffic accident, also suffering trauma to the right hemi body, multiple rib segmental fractures and hemothorax. After stabilization, he was taken to surgery for open reduction and internal fixation of the clavicle using a double plate technique, as it has been rarely described in the literature. The functional result was shown to be adequate and satisfactory in the postoperative follow-up. Despite the limited evidence available on the management of this type of pathology, surgical management is a valid option given the risk of non-union. The foregoing is concluded by the potential harm in patient functionality.

Experience with the Kosmos ultrasonographic tool in the approach and treatment of ambulatory patients of a heart failure clinic: a single-center cross-sectional study.

BACKGROUND: In Mexico, the epidemiology of heart failure is still not well understood. However, it is known that the primary cause of hospital admissions in patients with heart failure is pulmonary and systemic congestion. OBJECTIVE: To estimate congestion status and assess cardiac function using portable ultrasound in patients with heart failure. METHOD: A cross-sectional observational study was conducted. Patients who attended the Heart Failure Clinic at the Ignacio Chávez National Cardiology Institute in Mexico City between May and August 2022 were selected. They underwent ultrasonographic evaluation using a portable device to assess pulmonary and systemic congestion, as well as cardiac function and structure. RESULTS: One-hundred patients diagnosed with heart failure were prospectively included during the study period; 76% were male, with an average age of 59 years (range: 50-68 years). The recorded LVEF median was 34% (IQR: 27-43.5%). When evaluating pulmonary congestion, 78% of the patients showed a pattern A and 22% a pattern B. Following the VExUS protocol, 92% of the patients were at grade 0, 2% at grade 1, and 6% at grade 2. CONCLUSIONS: The use of the portable ultrasound facilitated the quantitative characterization of the echocardiographic features of the studied population. This device could provide better clinical characterization which, in turn, might allow for optimized drug prescription for heart failure and dose adjustments of diuretics based on echocardiographic congestion findings.

ANTECEDENTES: En México aún es muy poco conocida la epidemiología de la insuficiencia cardiaca, sin embargo se sabe que la principal causa de ingresos hospitalarios en los pacientes con insuficiencia cardiaca es la congestión pulmonar y sistémica. OBJETIVO: Estimar el estado de congestión y evaluar la función cardiaca mediante el ultrasonido portátil en pacientes con insuficiencia cardiaca tratados en un centro de tercer nivel en México. MÉTODO: Se llevó a cabo un estudio observacional transversal. Se seleccionaron pacientes que acudieron a la Clínica de Insuficiencia Cardiaca del Instituto Nacional de Cardiología Ignacio Chávez en la Ciudad de México entre mayo y agosto de 2022. Se les sometió a una evaluación ultrasonográfica mediante un dispositivo portátil para valorar la congestión pulmonar y sistémica, así como la función y estructura cardiaca. RESULTADOS: Se incluyeron de forma prospectiva 100 pacientes diagnosticados con insuficiencia cardiaca en el periodo de estudio. El 76% fueron hombres, con una edad mediana de 59 años (RIQ: 50-68 años). La mediana del FEVI registrada fue del 34% (RIQ: 27.0-43.5%). Al evaluar la congestión pulmonar, el 78% de los pacientes presentaron un patrón A y el 22% un patrón B. Siguiendo el protocolo VExUS, el 92% de los pacientes mostraron un grado 0, el 2% un grado 1 y el 6% un grado 2. CONCLUSIONES: El uso del ultrasonido portátil facilitó la caracterización cuantitativa de las características ecocardiográficas de la población estudiada. Este dispositivo podría ofrecer una mejor caracterización clínica que, a su vez, permita una optimización en la prescripción de medicamentos para la insuficiencia cardiaca y el ajuste de dosis de diuréticos según los hallazgos ecocardiográficos de congestión.

Personalized cardiovascular risk assessment in Rheumatoid Arthritis patients using circulating molecular profiles and their modulation by TNFi, IL6Ri, and JAKinibs.

BACKGROUND & OBJECTIVES: This study aimed to: 1) analyze the inflammatory profile of Rheumatoid Arthritis (RA) patients, identifying clinical phenotypes associated with cardiovascular (CV) risk; 2) evaluate biologic and targeted-synthetic disease-modifying antirheumatic drugs (b-DMARDs and ts-DMARDs': TNFi, IL6Ri, JAKinibs) effects; and 3) characterize molecular mechanisms in immune-cell activation and endothelial dysfunction. PATIENTS & METHODS: A total of 387 RA patients and 45 healthy donors were recruited, forming three cohorts: i) 208 RA patients with established disease but without previous CV events; ii) RA-CVD: 96 RA patients with CV events, and iii) 83 RA patients treated with b-DMARDs/ts-DMARDs for 6 months. Serum inflammatory profiles (cytokines/chemokines/growth factors) and NETosis/oxidative stress-linked biomolecules were evaluated. Mechanistic in vitro studies were performed on monocytes, neutrophils and endothelial cells (EC). RESULTS: In the first RA-cohort, unsupervised clustering unveiled three distinct groups: cluster 3 (C3) displayed the highest inflammatory profile, significant CV-risk score, and greater atheroma plaques prevalence. In contrast, cluster 1 (C1) exhibited the lowest inflammatory profile and CV risk score, while cluster 2 (C2) displayed an intermediate phenotype. Notably, 2nd cohort RA-CVD patients mirrored C3's inflammation. Treatment with b-DMARDs or ts-DMARDs effectively reduced disease-activity scores (DAS28) and restored normal biomolecules levels, controlling CV risk. In vitro, serum from C3-RA or RA-CVD patients increased neutrophils activity and CV-related protein levels in cultured monocytes and EC, which were partially prevented by pre-incubation with TNFi, IL6Ri, and JAKinibs. CONCLUSIONS: Overall, analyzing circulating molecular profiles in RA patients holds potential for personalized clinical management, addressing CV risk and assisting healthcare professionals in tailoring treatment, ultimately improving outcomes.

Hydrogen-Induced Reduction Improves the Photoelectrocatalytic Performance of Titania.

One of the main challenges to expand the use of titanium dioxide (titania) as a photocatalyst is related to its large band gap energy and the lack of an atomic scale description of the reduction mechanisms that may tailor the photocatalytic properties. We show that rutile TiO2 single crystals annealed in the presence of atomic hydrogen experience a strong reduction and structural rearrangement, yielding a material that exhibits enhanced light absorption, which extends from the ultraviolet to the near-infrared (NIR) spectral range, and improved photoelectrocatalytic performance. We demonstrate that both magnitudes behave oppositely: heavy/mild plasma reduction treatments lead to large/negligible spectral absorption changes and poor/enhanced (×10) photoelectrocatalytic performance, as judged from the higher photocurrent. To correlate the photoelectrochemical performance with the atomic and chemical structures of the hydrogen-reduced materials, we have modeled the process with in situ scanning tunneling microscopy measurements, which allow us to determine the initial stages of oxygen desorption and the desorption/diffusion of Ti atoms from the surface. This multiscale study opens a door toward improved materials for diverse applications such as more efficient rutile TiO2-based photoelectrocatalysts, green photothermal absorbers for solar energy applications, or NIR-sensing materials.

Whole genome assembly and annotation of the King Angelfish (Holacanthus passer) gives insight into the evolution of marine fishes of the Tropical Eastern Pacific.

Holacanthus angelfishes are some of the most iconic marine fishes of the Tropical Eastern Pacific (TEP). However, very limited genomic resources currently exist for the genus. In this study we: (i) assembled and annotated the nuclear genome of the King Angelfish (Holacanthus passer), and (ii) examined the demographic history of H. passer in the TEP. We generated 43.8 Gb of ONT and 97.3 Gb Illumina reads representing 75× and 167× coverage, respectively. The final genome assembly size was 583 Mb with a contig N50 of 5.7 Mb, which captured 97.5% of the complete Actinoterygii Benchmarking Universal Single-Copy Orthologs (BUSCOs). Repetitive elements accounted for 5.09% of the genome, and 33,889 protein-coding genes were predicted, of which 22,984 were functionally annotated. Our demographic analysis suggests that population expansions of H. passer occurred prior to the last glacial maximum (LGM) and were more likely shaped by events associated with the closure of the Isthmus of Panama. This result is surprising, given that most rapid population expansions in both freshwater and marine organisms have been reported to occur globally after the LGM. Overall, this annotated genome assembly provides a novel molecular resource to study the evolution of Holacanthus angelfishes, while facilitating research into local adaptation, speciation, and introgression in marine fishes.

A model-driven approach to upcycling recalcitrant feedstocks in Pseudomonas putida by decoupling PHA production from nutrient limitation.

Bacterial polyhydroxyalkanoates (PHAs) have emerged as promising eco-friendly alternatives to petroleum-based plastics since they are synthesized from renewable resources and offer exceptional properties. However, their production is limited to the stationary growth phase under nutrient-limited conditions, requiring customized strategies and costly two-phase bioprocesses. In this study, we tackle these challenges by employing a model-driven approach to reroute carbon flux and remove regulatory constraints using synthetic biology. We construct a collection of Pseudomonas putida-overproducing strains at the expense of plastics and lignin-related compounds using growth-coupling approaches. PHA production was successfully achieved during growth phase, resulting in the production of up to 46% PHA/cell dry weight while maintaining a balanced carbon-to-nitrogen ratio. Our strains are additionally validated under an upcycling scenario using enzymatically hydrolyzed polyethylene terephthalate as a feedstock. These findings have the potential to revolutionize PHA production and address the global plastic crisis by overcoming the complexities of traditional PHA production bioprocesses.

Hypersensitivity reaction to Abiraterone, successful desensitization protocol in prostate cancer patient.

INTRODUCTION: In prostate cancer, androgens are key in the growth of both normal prostate and cancer cells. Abiraterone acetate inhibits CYP17, an important target in prostate cancer given its central role in the production of adrenal and tumor-derived androgens. Although abiraterone is generally well tolerated, common adverse effects such as hypertension, hypokalemia, and hepatotoxicity have been reported. CLINICAL CASE: We present the case of an 83-year-old Mexican man with high-volume EC IV prostate cancer resistant to castration, orchiectomy, and bone, liver, and lung metastases. First-line treatment with the CHAARTED scheme was indicated, by patient decision refuse chemotherapy treatment. On the fourth day of starting treatment, he developed pruritic erythematous macular skin lesions and urticaria on the posterior chest that resolved spontaneously. A generalized erythematous and pruritic maculopapular rash appeared 12 days after starting abiraterone, for which she was referred to allergies. MANAGEMENT AND RESULTS: An oral provocation test was performed for two days, presenting localized macular lesions eight hours after the administration of abiraterone. An oral desensitization protocol was carried out for ten days in which no hypersensitivity reactions were observed, thus achieving the successful administration of abiraterone.

Comparison of Mechanical Insufflation-Exsufflation and Hypertonic Saline and Hyaluronic Acid With Conventional Open Catheter Suctioning in Intubated Patients.

BACKGROUND: Open respiratory secretion suctioning with a catheter causes pain and tracheobronchial mucosal injury in intubated patients. The goal of mechanical insufflation-exsufflation (MI-E) is to move secretions proximally and noninvasively by generating a high peak expiratory air flow. Nebulized hypertonic saline with hyaluronic acid (HS-HA) may facilitate suctioning by hydration. We assessed the safety and tolerance of a single session of airway clearance with MI-E and HS-HA in critically ill intubated patients. METHODS: Adults with a cuffed artificial airway were randomized to (1) open suctioning, (2) open suctioning after HS-HA, (3) MI-E, or (4) MI-E with HS-HA. Adverse events, pain and sedation/agitation scores, and respiratory and hemodynamic variables were collected before, during, and 5-min and 60-min post intervention. RESULTS: One-hundred twenty subjects were enrolled and completed the study. Median (interquartile range [IQR]) Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 22 (16-28); median (IQR) age was 69.0 (57.0-75.7) y, and 90 (75%) were male. Baseline respiratory and hemodynamic variables were comparable. Adverse events occurred in 30 subjects (25%), with no between-group differences. Behavioral pain equivalents and Richmond Agitation-Sedation Scale were higher during suctioning in groups 1 (P < .001) and 2 (P < .001). Independent predictive variables for higher pain and agitation/sedation scores were study groups 1 and 2 and simultaneous analgosedation, respectively. Noradrenaline infusion rates were lower at 60 min in groups 2 and 4. PaO2 /FIO2 had decreased at 5 min after open suctioning in group 1 and increased at 60 min in group 3. CONCLUSIONS: We observed no difference in adverse events. MI-E avoids pain and agitation.