Search

Introduction: In the rapidly advancing field of 'omics research, there is an increasing demand for sophisticated bioinformatic tools to enable efficient and consistent data analysis. As biological datasets, particularly metabolomics, become larger and more complex, innovative strategies are essential for deciphering the intricate molecular and cellular networks. Methods: We introduce a pioneering analytical approach that combines Principal Component Analysis (PCA) with Graphical Lasso (GLASSO). This method is designed to reduce the dimensionality of large datasets while preserving significant variance. For the first time, we applied the PCA-GLASSO algorithm (i.e., MetaboLINK) to metabolomics data derived from Nuclear Magnetic Resonance (NMR) spectroscopy performed on neural cells at various developmental stages, from human embryonic stem cells to neurons. Results: The MetaboLINK analysis of longitudinal metabolomics data has revealed distinct pathways related to amino acids, lipids, and energy metabolism, uniquely associated with specific cell progenies. These findings suggest that different metabolic pathways play a critical role at different stages of cellular development, each contributing to diverse cellular functions. Discussion: Our study demonstrates the efficacy of the MetaboLINK approach in analyzing NMR-based longitudinal metabolomic datasets, highlighting key metabolic shifts during cellular transitions. We share the methodology and the code to advance general 'omics research, providing a powerful tool for dissecting large datasets in neurobiology and other fields. [ABSTRACT FROM AUTHOR]

Objective: To assess the relationship between smoking exposure and organ damage accrual measured by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for Systemic Lupus Erythematosus score (SLICC-SDI) in consecutive patients with systemic lupus erythematosus (SLE) from Argentina. Methods: 623 consecutive SLE patients (fulfilling ≥4, 1997 ACR criteria) were included in this cross-sectional study. Sociodemographic and disease related variables including SLICC-SDI score and smoking status were collected. Patients currently smoking were considered "smokers", and "non-smokers" those who never smoked and former smokers. SLICC-SDI was divided into two categories: <3 and ≥3 was defined as severe damage. Results: Six hundred and 23 patients were included in the analysis, 89% women. Eighty-four per cent were non-smokers and 16 % were current smokers 83 percent of patients had SLICC-SDI <3 and 17 % had SLICC-SDI ≥3. Twenty one percent of patients with SLICC-SDI ≥3 and 15% with <3 SLICC-SDI were current smokers (p 0.081). In the multiple regression analysis, current smoking (OR 1.82, CI 95% 1.01-3.31, p 0.046), older age (OR 1.04, CI 95% 1.00-1.05, p 0.034), disease duration (OR 1.03, CI 95% 1.00-1.07, p 0.021) and cyclophosphamide exposure (OR 2.97, CI 95% 1.49-5.88, p 0.002) were related to SLICC-SDI ≥3. Conclusion: In our sample of patients, current smoking, older age, disease duration and cyclophosphamide were related to severe damage (SLICC-SDI ≥3). [ABSTRACT FROM AUTHOR]

The JUpiter Icy Moon Explorer (JUICE) mission, launched on 14 April 2023, aims to explore Jupiter and its Galilean moons, with arrival in the Jovian system planned for mid-2031. One of the scientific investigations is the Geodesy and Geophysics of Jupiter and the Galilean Moons (3GM) radio science experiment, designed to study the interior structures of Europa, Callisto, and Ganymede and the atmospheres of Jupiter and the Galilean moons. The 3GM experiment employs a Ka-band Transponder (KaT) to enable two-way coherent range and Doppler measurements used for the gravity experiment and an Ultra Stable Oscillator (USO) for one-way downlink occultation experiments. This paper analyzes KaT data collected at the ESA/ESTRACK ground station in Malargüe, Argentina, during the Near-Earth Commissioning Phase (NECP) in May 2023 and the first in-cruise payload checkout (PC01) in January 2024. The radiometric data were fitted using both NASA's Mission Analysis, Operations, and Navigation Toolkit Environment (MONTE) and ESA's General Orbit Determination and Optimization Toolkit (GODOT) software. The comparison of the orbital solutions showed an excellent agreement. In addition, the Doppler and range residuals allowed a preliminary assessment of the quality of the radiometric measurements. During the NECP pass, the radio link data showed a range-rate noise of 0.012 mm/s at 1000 s integration time, while the root mean square of the range residuals sampled at 1 s was 8.4 mm. During the first payload checkout, the signal power at the KaT input closely matched the value expected at Jupiter, due to a specific ground station setup. This provided early indications of the 3GM's performance during the Jovian phase. In this test, the accuracy of range data at an integration time of 1s, particularly sensitive to the link signal-to-noise ratio, degraded to 13.6 cm, whilst the range-rate accuracy turned out to be better than 0.003 mm/s at 1000 s, thanks to the accurate tropospheric delay calibration system (TDCS) available at the Malargue station (inactive during NECP). [ABSTRACT FROM AUTHOR]

Background: Fatigue is a prevalent and complex condition with significant impacts on well-being. Existing fatigue assessments often lack comprehensiveness or practicality for general population studies. Methods: This study validated the REST Questionnaire, a novel fatigue assessment tool, in a sample of 268 adults. Psychometric properties, including internal consistency and construct validity, were evaluated. REST scores were correlated with WHO-5 well-being, BMI, self-rated health, and chronic conditions. Exploratory factor analysis identified underlying dimensions of fatigue. Results: The REST Questionnaire demonstrated excellent internal consistency (Cronbach's alpha = 0.918) and construct validity. Higher fatigue scores were associated with lower well-being, female gender, and the presence of certain chronic conditions (cancer, kidney stones, gastric ulcers). Two distinct fatigue dimensions, "physical fatigue and functional impacts" and "emotional and social consequences", were identified. Conclusions: The REST Questionnaire is a reliable and valid tool for assessing fatigue in the general population. Its multidimensional framework and sensitivity to comorbidities offer valuable insights for research and public health applications, with the potential to inform targeted interventions aimed at improving well-being. [ABSTRACT FROM AUTHOR]

Copyright of Retos: Nuevas Perspectivas de Educación Física, Deporte y Recreación is the property of Federacion Espanola de Asociaciones de Docentes de Educacion Fisica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Despite an improved understanding of its pathogenesis, dry eye disease (DED) remains relatively underestimated and its treatment challenging. A better alignment between the clinical evaluation and the patient self-assessment also requires capturing the whole patient experience of DED. This project aimed to unveil this experience through narrative medicine (NM). Methods: The project involved 38 expert centres in Italy and one in San Marino, targeting adult patients with DED, their informal caregivers and their treating ophthalmologists. Written narratives and sociodemographic and quality of life (QoL)-related data were anonymously collected through the project's webpage. Narratives were analysed through MAXQDA (VERBI Software, Berlin, Germany), NM classifications and content analysis. Results: A total of 171 patients with DED, 37 informal caregivers and 81 ophthalmologists participated in the research. DED was defined as a disabling condition by 19% of patients and 35% of caregivers; 70% of patients reported that a therapeutic alliance is an integral part of DED treatment and 32% hope for more effective therapies. Forty-four per cent of patients assessed their own QoL as good; however, DED emerged as importantly impacting work performance and social events. DED physical, emotional and economic burden and the cruciality of a trusting care relationship represent the main themes that emerged across all narratives, while empathy and effective treatment are among the factors favouring coping with DED. Conclusion: This project marked a pioneering initiative investigating the lived experience of patients with DED through NM, simultaneously involving all viewpoints involved in the care pathway. NM enabled the unveiling of factors favouring the ability to cope with DED and its associated QoL implications and provided valuable insights to improve the therapeutic alliance. [ABSTRACT FROM AUTHOR]

Background: Despite the effectiveness of inhalation therapy, uncontrolled or severe asthma remains prevalent challenges in respiratory care Narrative Medicine (NM) offers a linguistic approach to comprehending illness experiences, thereby providing a framework for advancing healthcare. Aim: The primary aim of this study was to gather narratives from individuals grappling with severe or uncontrolled asthma and their Healthcare Professionals (HCPs), in order to explore the intricate interplay among quality of care, quality of life, psychological and social determinants, and adherence patterns. Methods: A cross-sectional NM study was conducted in Italy from February to December 2023, encompassing 135 patients with uncontrolled or severe asthma (54.7% male; mean age: 56.7 years) and 47 HCPs (64.9% male; mean age: 54.3 years). A mixed-method approach was adopted to scrutinize themes, language nuances, emotional expressions, and narrative classifications. Results: Patients with uncontrolled or severe asthma reported an average illness duration of 4.46 years, with exacerbations occurring over the past 20.9 months. Pulmonologists (83% of HCPs) played a predominant role in diagnosing and treating the disease in 96.1% of patients. Additionally, participants with severe asthma reported higher healthcare needs. The most reported emotions were fatigue (25.96%) and a sense of suffocation (11.53%). Upon commencing treatment, while experiencing physical improvement, patients predominantly expressed feelings of "submission/dependence" on medication (28%), followed by "fear" (21%) and "serenity/joy" (21%). HCPs, primarily pulmonologists (83%), emphasized the importance of raising awareness among specialists and General Practitioners (GPs), disseminating information, optimizing prescriptions, implementing phenotyping, tailoring therapy, and considering paediatric needs. Conclusion: These findings contribute to a deeper understanding of patient perspectives, facilitate personalized interventions, and underscore the factors influencing therapeutic adherence in uncontrolled or severe asthma. [ABSTRACT FROM AUTHOR]

Haploinsufficiency of FOXP1 gene is responsible for a neurodevelopmental disorder presenting with intellectual disability (ID), autism spectrum disorder (ASD), hypotonia, mild dysmorphic features, and multiple congenital anomalies. Joint contractures are not listed as a major feature of FOXP1‐related disorder. We report five unrelated individuals, each harboring likely gene disruptive de novo FOXP1 variants or whole gene microdeletion, who showed multiple joint contractures affecting at least two proximal and/or distal joints. Consistent with the phenotype of FOXP1‐related disorder, all five patients showed developmental delay with moderate‐to‐severe speech delay, ID, ASD, and facial dysmorphic features. FOXP1 is implicated in neuronal differentiation and in organizing motor axon projections, thus providing a potential developmental basis for the joint contractures. The combination of joint contractures and neurodevelopmental disorders supports the clinical suspicion of FOXP1‐related phenotype. [ABSTRACT FROM AUTHOR]

Biosensors stand at the forefront of innovation in critical fields such as medicine, food safety, and environmental monitoring, offering precise detection of specific biomarkers. Among these, polymer-based biosensors have emerged as powerful tools, evolving from inert materials to intricately tailored structures capable of precise molecular binding. Electrospinning, a prominent fabrication method, offers a cost-effective approach for developing diagnostic kits, pushing the boundaries of biosensors with exceptionally low analyte detection limits. However, the reliance on commercial polymers restricts the versatility of electrospun nanofibers due to the fixed properties and limited functionalization options of off-the-shelf materials. These constraints prevent the tailoring of nanofibers to meet specific or diverse needs, as their molecular structure and surface functionalities are not easily adjustable. A promising solution is integrating Controlled Radical Polymerization (CRP) with electrospinning. CRP provides precise control over polymer properties, enabling the creation of nanofibers with customized functionalities for various applications. This approach combines the benefits of electrospinning, such as high surface area-to-volume ratios, with the advanced capabilities of CRP to enhance the selectivity and sensitivity of biosensors. This review represents recent advancements in biosensors, covering acquisition, characterization, and applications, with a focal point on the role of functional polymers. Exploring biosensor architecture, electrospinning principles, controlled polymer synthesis, CRP techniques, and polymer topologies, the manuscript also discusses challenges and future prospects, including microfluidic integration, multi-detection capabilities, machine learning, and the development of wearable biosensors. [ABSTRACT FROM AUTHOR]

Introduction: Infliximab (IFX) is a standard, inpatient salvage therapy for the treatment of refractory acute severe ulcerative colitis (ASUC). Remicade™ is the originator IFX. Its biosimilar Renflexis™ offers a reduced cost structure. We performed a cost-minimization analysis to compare costs with Remicade™ and Renflexis™ for the inpatient treatment of ASUC. Methods: Retrospective clinical and financial data were obtained from 34 inpatients with refractory ASUC who received Renflexis™ (n = 17) or Remicade™ (n = 17) between 2019 and 2021. Clinical data included admission and discharge laboratory values. Financial data included a decision support drug cost (DSDC), constituting the total cost associated with inpatient IFX administration, and total inpatient cost of care. The following equation generated a ratio (rDSDC) representing the percentage of drug cost (or DSDC) of the total inpatient cost of care, after controlling for IFX dose and length of stay: [DSDC of IFX/Number of Units of IFX] ÷ [Total Inpatient Cost of Care/Length of Stay in Days]. Median and non-parametric Wilcoxon ranked sum test were used for analyzing patient demographics, clinical, and financial data. Results: No differences were found in baseline or discharge clinical parameters. The median unadjusted ratio of DSDC to total inpatient cost of care was 0.387 versus 0.241 in the Remicade™ versus Renflexis™ groups (p = 0.0025), respectively, representing an absolute difference of ∼14%. Median adjusted rDSDC were 0.04 versus 0.024 in the Remicade™ versus Renflexis™ groups, respectively, representing a relative cost reduction of ∼40% (p = 0.0001). Discussion: The unadjusted absolute cost reduction and adjusted relative cost reduction were, respectively, 14% and 40% in the Renflexis™ group as compared to Remicade™, when treating inpatient ASUC. Our calculation included median DSDC as a percentage of the total inpatient cost of care, controlling for IFX dose and length of stay. This reduced cost structure promotes use of Renflexis™ for ASUC inpatients and may reduce costs systemically. [ABSTRACT FROM AUTHOR]

Available data highlights the significant impact of the COVID-19 pandemic on global vaccination trends. Despite this, comprehensive evaluations of these changes at the European level are still scarce. This study examines coverage for diphtheria, tetanus, and pertussis (DTP) and measles-containing vaccines (MCV) in the WHO European Region from 2000 to 2022. Vaccination coverage data, defined as the percentage of surviving infants who received the first and third doses of DTP (DTP1 and DTP3) and the first and second doses of MCV (MCV1 and MCV2), were extracted from UNICEF databases. Joinpoint regression analysis was employed to identify joinpoints in the time series and to estimate Annual Percent Changes (APCs) and Average Annual Percent Changes (AAPCs) over predefined timeframes. The coverages for DTP1 and MCV1 exhibit a similar trend, overall characterized by four joinpoints, one of which is in 2019. In contrast, the coverage for DTP3 does not show a significant temporal trend and lacks joinpoints, while the vaccination coverage for MCV2 shows a steadily increasing trend, with three identified joinpoints. A comparative analysis with the pre-pandemic period reveals a significant increase in the number of countries characterized by a decreasing trend during the pandemic period for all considered vaccination coverages, as indicated by the negative AAPC values. These results highlight the effect of the pandemic on childhood vaccination coverage. Compared to a mere descriptive analysis, the temporal analysis of trends using joinpoint regression provides significant opportunities to identify variations in vaccination coverages and pinpoint areas for intervention in future vaccination strategies. [ABSTRACT FROM AUTHOR]

A radio link directly probing the inner solar corona offers the possibility to characterize solar wind properties, including velocity, density, turbulence, and even the axial ratio. In this study, we leveraged radiometric data obtained during a joint superior solar conjunction of the ESA/JAXA BepiColombo mission and the JAXA Akatsuki mission. Our objective is to ascertain the solar wind velocity by analysing Doppler-shift timeseries of radio signals exchanged between the two spacecraft and two distinct ground stations. We conducted a cross-correlation analysis to determine the travel time of large-scale plasma density fluctuations as they intersect with the downlink signals of both spacecraft. This method is applied to the data collected on 2021 March 13 and 2021 March 14. The analysis of the March 13 data has shown that the two Doppler residuals timeseries present a clear correlation at a time-lag of 2910 s. Using the knowledge of the relative distance between the two probe-ground station lines of sight at the closest approach to the Sun, we estimated the solar wind velocity to be |$421\pm 21$| km s−1. Following the same procedure for the second experiment, we estimated the solar wind speed velocity to be |$336\pm 7$| km s−1. These results are compatible with the sampling of the slow solar wind at heliographic latitudes of |$-22^\circ$| and |$-26^\circ$|⁠ , respectively. [ABSTRACT FROM AUTHOR]

Extra pancreatic manifestations of pancreatitis are rare, with a prevalence of 2–3%. One such rare manifestation is the triad of joint pain (polyarthritis), tender skin lesions (panniculitis), and pancreatic inflammation (pancreatitis), known as PPP. The pathogenesis of this phenomenon is not fully understood but is believed to involve lipolysis by pancreatic enzymes at lipid-rich skin and joint sites. PPP primarily affects middle-aged males with a history of alcohol use disorder. Diagnosis can be challenging due to the absence of typical abdominal symptoms. Delayed diagnosis may significantly worsen outcomes. Supportive therapy is the mainstay, but resolution requires addressing the underlying pancreatic abnormality. We present a case of a patient with a history of alcohol use disorder and recurrent acute pancreatitis who developed joint pain and skin rash. Extensive work-up ruled out other causes, and imaging and biopsy confirmed the diagnosis of PPP. Symptomatic management and treatment of the underlying pancreatic abnormality led to complete resolution of symptoms. Our case serves to raise awareness of this rare but potentially fatal syndrome. [ABSTRACT FROM AUTHOR]

The article focuses on the role of instant messaging in cancer care, particularly its potential to enhance doctor-patient communication. Topics discussed include the effectiveness of text messaging for preventive health behaviors, the impact of bidirectional communication on patient outcomes, and the challenges of continuous availability for healthcare professionals.

The analysis of altimetric profiles in Antarctica and their evolution over the years is a sensitive topic for the scientific community since it helps understand the effects of climate change that the continent undergoes. Different geomatic techniques, including the GNSS technology, can be employed to obtain altimetric profiles. However, the GNSS differenced approaches, such as the Post Processing Kinematic, are hardly usable to define long profiles in Antarctica because of the low number of CORS stations. In these conditions, the Precise Point Positioning (PPP) approach is a valid alternative to avoid processing very long baselines. The aim of this article is to define a standard procedure for the processing of historical GPS data, thanks to the availability of a dataset from the International Trans-Antarctic Scientific Expedition, which took place between 1998 and 1999 (ITASE98-99). This expedition focused on mapping the Antarctic territory, subdividing it by nations of influence, using geophysical and geodetic technologies, including GPS. The altimetric profiles had already been calculated in 2002 by the Geomatics group of the University of Bologna using the Gipsy-OASIS II software. In this work, the new version of the JPL software, GipsyX, is used to apply the newly implemented models and reprocessed products. The calibration of the processing parameters leading to the final PPP solution is described in the paper, including details on the implementation of a post-processing filtering procedure. The average a posteriori elevation error is 4.6 cm, while 99% of them are within 27 cm. The comparison of the new results to both the previous processing and the REMA elevation model shown that about double the number of solutions are now available, meter-level elevation spikes have been avoided, and a half meter bias is now reduced to a few centimeters. Given the almost 15 years difference between the 1999.0 expedition epoch and the REMA reference epoch, the obtained results can be used to study accumulation/erosion effects on the Antarctica ice sheet. [ABSTRACT FROM AUTHOR]

Questions: Marine rocky outcrops are model systems of community assembly under harsh conditions. The prevailing environmental conditions that determine a coast–inland gradient of stress and disturbance impose a strong environmental filter on community assembly. However, the Atlantic rocky outcrops of Uruguay challenge this assumption as they exhibit high plant diversity at small spatial scales. We investigated this study system to answer: (1) which environmental factors determine diversity at the local scale; (2) and how does the regional pool influence species composition along the coast–inland gradient? Methods: We analyzed the local and regional determinants of plant community assembly in four rocky sites along the Uruguayan coast. Through a random sampling approach stratified by distance to the coast, we recorded species occurrences and microenvironmental conditions. Observed taxa were assigned into different species assemblages according to their typical vegetation type. Generalized Linear Model (GLM)–Poisson regression, quantile regressions and hierarchical cluster analyses were used to identify the factors underlying local richness and the spatial vegetation structure. Results: Nine different vegetation types generate a mass effect that enhances local diversity. Unexpectedly, 56% of the species are from non‐marine environments — e.g. grasslands or hydrophilous herblands. Species assemblages were spatially clustered, with a turnover of these clusters along the coast–inland gradient. Elevation, distance to the coast and vegetation cover promoted richness, likely due to an attenuation of marine filters. Meanwhile, substrate availability reduced richness, likely due to competitive exclusion as a result of more resources and homogeneous microenvironmental conditions. Conclusions: The high local diversity along the marine rocky outcrops of Uruguay is best explained by a functionally diverse regional species pool, which interacts with local heterogeneity, and by conditions that enhance or attenuate the effect of marine stress. Effective conservation and management strategies are key to minimize the detrimental effects of urbanization, fragmentation, and non‐native plant invasions on these diverse habitats. [ABSTRACT FROM AUTHOR]

Background: Acute liver injury occurs most frequently due to trauma, but it can also occur because of sepsis or drug-induced injury. This review aims to analyze artificial intelligence (AI)'s ability to detect and quantify liver injured areas in adults and pediatric patients. Methods: A literature analysis was performed on the PubMed Dataset. We selected original articles published from 2018 to 2023 and cohorts with ≥10 adults or pediatric patients. Results: Six studies counting 564 patients were collected, including 170 (30%) children and 394 adults. Four (66%) articles reported AI application after liver trauma, one (17%) after sepsis, and one (17%) due to chemotherapy. In five (83%) studies, Computed Tomography was performed, while in one (17%), FAST-UltraSound was performed. The studies reported a high diagnostic performance; in particular, three studies reported a specificity rate > 80%. Conclusions: Radiomics models seem reliable and applicable to clinical practice in patients affected by acute liver injury. Further studies are required to achieve larger validation cohorts. [ABSTRACT FROM AUTHOR]

Bladder cancer is considered a global health concern characterized by significant morbidity and mortality rates. The complex relationship between diet and bladder cancer is examined, with a specific focus on the role of diet in risk, outcomes, and treatment efficacy. Attention is drawn to the burgeoning field of immunotherapy in bladder cancer treatment, and the possible influence of diet on its outcomes is explored. While evidence remains limited, prior studies in other cancer types have suggested a potential connection between diet and immunotherapy response. To address this knowledge gap, the ongoing BLOSSOM study is presented, which aims to investigate the link between dietary factors, lifestyle, and the effectiveness of immunotherapy in patients with non-muscle-invasive bladder cancer. Ongoing efforts to decipher the intricate relationship between diet and bladder cancer care are highlighted, emphasizing the quest to unravel the dietary puzzle for the improvement of bladder cancer management. [ABSTRACT FROM AUTHOR]

We introduce the notion of Tolerance for autonomous artificial agents (and its antithetical concept, Intolerance), motivating its theoretical adoption in the fields of social robotics and human—agent interaction, where it can effectively complement two contiguous, but essentially distinct, constructs—Acceptance and Trust—that are broadly used by researchers. We offer a comprehensive conceptual model of Tolerance, construed as a user's insusceptibility or resilience to Autonomy Estrangement (i.e., the uncanny sense of isolation and displacement experienced by the humans who believe, for right or wrong reasons, that robots can subvert and/or control their lives). We also refer to Intolerance to indicate the opposite property, that is the user's susceptibility or proneness to Autonomy Estrangement. Thus, Tolerance and Intolerance are inverse representations of the same phenomenological continuum, with Intolerance increasing when Tolerance decreases and vice versa. While Acceptance and Trust measure how the user's interaction with a particular robot is satisfying and efficacious, the dyad Tolerance/Intolerance reflects how the user's attitude is affected by deeply held normative beliefs about robots in general. So defined, a low Tolerance (that is a high Intolerance) is expected to correlate to antagonistic responses toward the prospect of adoption: specifically, Intolerant attitudes predict the kind of anxious and hostile behaviours toward Agents that originate from the concerns that autonomous systems could deeply disrupt the lives of humans (affecting their work cultures, ways of living, systems of values, etc.) or dominate them (making humans redundant, undermining their authority, threatening their uniqueness, etc.). Thus, Negative beliefs and worldviews about Agents are the cause of the Intolerant attitude toward Agents, which predicts Autonomy Estrangement, which in turn correlates to low Adoption Propensity and avoidance and rejection behaviours. [ABSTRACT FROM AUTHOR]

This study investigated the impact of overexpressing the mitochondrial enzyme Fumarylacetoacetate hydrolase domain-containing protein 1 (FAHD1) in human osteosarcoma epithelial cells (U2OS) in vitro. While the downregulation or knockdown of FAHD1 has been extensively researched in various cell types, this study aimed to pioneer the exploration of how increased catalytic activity of human FAHD1 isoform 1 (hFAHD1.1) affects human cell metabolism. Our hypothesis posited that elevation in FAHD1 activity would lead to depletion of mitochondrial oxaloacetate levels. This depletion could potentially result in a decrease in the flux of the tricarboxylic acid (TCA) cycle, thereby accompanied by reduced ROS production. In addition to hFAHD1.1 overexpression, stable U2OS cell lines were established overexpressing a catalytically enhanced variant (T192S) and a loss-of-function variant (K123A) of hFAHD1. It is noteworthy that homologs of the T192S variant are present in animals exhibiting increased resistance to oxidative stress and cancer. Our findings demonstrate that heightened activity of the mitochondrial enzyme FAHD1 decreases cellular ROS levels in U2OS cells. However, these results also prompt a series of intriguing questions regarding the potential role of FAHD1 in mitochondrial metabolism and cellular development. [ABSTRACT FROM AUTHOR]

Bioactive compounds blended with synthetic polymers constitute an effective alternative for tailored materials design in advanced applications. Biological functionalities are easily incorporated, and the materials' overall performance can be improved using this technique. The present work introduces the production and characterization of electrospun scaffolds comprised poly(vinyl alcohol), chitosan, and oligo(β-pinene) with potential for tissue engineering. Oligo(β-pinene) presents many biological functionalities of interest, especially cytoprotective activity. The scaffolds' structure, processing, properties, and performance relationships were evaluated. The materials presented an average fiber diameter of 159 nm, which was increased with the oligo(β-pinene) addition in the polymer matrix. There was an overall trend of crystallinity decrease (from 21.02 to 6.4%) with the incorporation of the oligomer. The polymers' ∆Hm and Tm increased from 28.43 to 35.51 J g−1 and from 190.54 to 194.10 °C, respectively, with the addition of oligo(β-pinene). The presence of a few fiber defects appeared upon oligomer inclusion. However, the overall thermal performance of the scaffolds improved with the increase in oligo(β-pinene) content on the nanofibers. Essays of cell proliferation revealed significant benefits from oligo(β-pinene) inclusion on the blends tested. Biocompatibility improvement of up to 21.5% was noted compared to the control. Thus, incorporating oligo(β-pinene) in poly(vinyl alcohol)-chitosan electrospun nanofibers constitutes a renewable option to enhance the scaffolds' properties and biocompatibility. [ABSTRACT FROM AUTHOR]

The exploration of Uranus, a key archetype for ice giant planets and a gateway to understanding distant exoplanets, is acquiring increasing interest in recent years, especially after the Uranus Orbiter and Probe (UOP) mission has been prioritized in the Planetary Science Decadal Survey 2023–2032. This paper presents the results of numerical simulations aimed at providing experimental constraints on the parameterized post-Newtonian (PPN) parameter γ , a measure of space–time curvature in general relativity (GR), during the cruise phase of a spacecraft travelling to Uranus. Leveraging advanced radio tracking systems akin to those aboard the JUICE and BepiColombo missions, we explore the potential of solar conjunction experiments (SCEs) to refine current measurements of γ by exploiting the spacecraft's long journey in the outer Solar System. We discuss the anticipated enhancements over previous estimates, underscoring the prospect of detecting violations of GR. Our simulations predict that by using an advanced radio tracking system, it is possible to obtain an improvement in the estimation of γ up to more than an order of magnitude with respect to the latest measurement performed by the Cassini–Huygens mission in 2002, contingent on the calibration capabilities against solar plasma noise. The results reveal that a number of SCEs during the mission can substantially strengthen the validation of GR. In tandem with fundamental physics tests, the use of radio links during SCEs presents a valuable opportunity to dissect the solar corona's plasma dynamics, contributing to solar physics and space weather forecasting. This paper also enumerates methodologies to analyze electron density, localize plasma features, and deduce solar wind velocity, enriching the scientific yield of the experiments beyond the primary objective of testing GR during the cruise phase of a mission to Uranus. [ABSTRACT FROM AUTHOR]

Background: Artificial Intelligence (AI)-based analysis represents an evolving medical field. In the last few decades, several studies have reported the diagnostic efficiency of AI applied to Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) to early detect liver metastases (LM), mainly from colorectal cancer. Despite the increase in information and the development of different procedures in several radiological fields, an accurate method of predicting LM has not yet been found. This review aims to compare the diagnostic efficiency of different AI methods in the literature according to accuracy, sensibility, precision, and recall to identify early LM. Methods: A narrative review of the literature was conducted on PubMed. A total of 336 studies were screened. Results: We selected 17 studies from 2012 to 2022. In total, 14,475 patients were included, and more than 95% were affected by colorectal cancer. The most frequently used imaging tool to early detect LM was found to be CT (58%), while MRI was used in three cases. Four different AI analyses were used: deep learning, radiomics, machine learning, and fuzzy systems in seven (41.18%), five (29.41%), four (23.53%), and one (5.88%) cases, respectively. Four studies achieved an accuracy of more than 90% after MRI and CT scan acquisition, while just two reported a recall rate ≥90% (one method using MRI and CT and one CT). Conclusions: Routinely acquired radiological images could be used for AI-based analysis to early detect LM. Simultaneous use of radiomics and machine learning analysis applied to MRI or CT images should be an effective method considering the better results achieved in the clinical scenario. [ABSTRACT FROM AUTHOR]

We present the case of a 36-year-old primigravida who gave birth to a 3200 g baby by vacuum-assisted (Kiwi OmniCup™) operative vaginal delivery with mediolateral episiotomy. A "y"-shaped perineal tear with a grade IIIC obstetric anal sphincter injury (OASI) was diagnosed and repaired. Two days after delivery, in the absence of suture dehiscence, she started experiencing complete anal incontinence. A decision was made in association with a proctologic surgeon for an early secondary repair. Before surgery, a Three-dimensional transperineal ultrasound (TPUS) was performed. The exam revealed a major defect of the external anal sphincter at the 11 o'clock position. This allowed for the reopening of only a circumscribed area of the perineal suture and repair of the sphincters using the end-to-end technique. The symptoms regressed completely, and follow-up TPUS demonstrated the gradual wound healing process. Anal incontinence, secondary to obstetric anal sphincter injury (OASI), has a severe negative impact on women's quality of life. TPUS is an effective method to detect sphincter defects and monitor the healing process. This report investigates the feasibility of identifying the sphincter tear in an incontinent puerperal patient without suture dehiscence in order to target early secondary repair while minimizing its extent. TPUS has proven a safe and effective tool to guide early secondary repair of symptomatic OASI complications while minimizing the invasiveness of the procedure. Multidisciplinary management is crucial to ensure the adequate standard of care. [ABSTRACT FROM AUTHOR]

N-methyl-d-aspartate receptors (NMDARs) are members of the glutamate receptor family and participate in excitatory postsynaptic transmission throughout the central nervous system. Genetic variants in GRIN genes encoding NMDAR subunits are associated with a spectrum of neurological disorders. The M3 transmembrane helices of the NMDAR couple directly to the agonist-binding domains and form a helical bundle crossing in the closed receptors that occludes the pore. The M3 functions as a transduction element whose conformational change couples ligand binding to opening of an ion conducting pore. In this study, we report the functional consequences of 48 de novo missense variants in GRIN1, GRIN2A, and GRIN2B that alter residues in the M3 transmembrane helix. These de novo variants were identified in children with neurological and neuropsychiatric disorders including epilepsy, developmental delay, intellectual disability, hypotonia and attention deficit hyperactivity disorder. All 48 variants in M3 for which comprehensive testing was completed produce a gain-of-function (28/48) compared to loss-of-function (9/48); 11 variants had an indeterminant phenotype. This supports the idea that a key structural feature of the M3 gate exists to stabilize the closed state so that agonist binding can drive channel opening. Given that most M3 variants enhance channel gating, we assessed the potency of FDA-approved NMDAR channel blockers on these variant receptors. These data provide new insight into the structure–function relationship of the NMDAR gate, and suggest that variants within the M3 transmembrane helix produce a gain-of-function. [ABSTRACT FROM AUTHOR]

Colorectal cancer is a frequent neoplasm in western countries, mainly due to dietary and behavioral factors. Its incidence is growing in developing countries for the westernization of foods and lifestyles. An increased incidence rate is observed in patients under 45 years of age. In recent years, the mortality for CRC is decreased, but this trend is slowing. The mortality rate is reducing in those countries where prevention and treatments have been implemented. The survival is increased to over 65%. This trend reflects earlier detection of CRC through routine clinical examinations and screening, more accurate staging through advances in imaging, improvements in surgical techniques, and advances in chemotherapy and radiation. The most important predictor of survival is the stage at diagnosis. The screening programs are able to reduce incidence and mortality rates of CRC. The aim of this paper is to provide a comprehensive overview of incidence, mortality, and survival rate for CRC. [ABSTRACT FROM AUTHOR]

Copyright of Form@re is the property of Firenze University Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To inform strategies aimed at improving blood pressure (BP) control and reducing salt intake, we assessed educational inequalities in high blood pressure (HBP) awareness, treatment and control; physician's advice on salt reduction; and salt knowledge, perceptions and consumption behaviours in Eastern Europe and Central Asia. Design: Data were collected in cross-sectional, population-based nationally representative surveys, using a multi-stage clustered sampling design. Five HBP awareness, treatment and control categories were created from measured BP and hypertension medication use. Education and other variables were self-reported. Weighted multinomial mixed-effects regression models, adjusted for confounders, were used to assess differences across education categories. Settings: Nine Eastern European and Central Asian countries (Armenia, Azerbaijan, Belarus, Georgia, Kyrgyzstan, Republic of Moldova, Tajikistan, Turkey and Uzbekistan). Participants: Nationally representative samples of 30 455 adults aged 25–65 years. Results: HBP awareness, treatment and control varied substantially by education. The coverage of physician's advice on salt was less frequent among participants with lower education, and those with untreated HBP or unaware of their HBP. The education gradient was evident in salt knowledge and perceptions of salt intake but not in salt consumption behaviours. Improved salt knowledge and perceptions were more prevalent among participants who received physician's advice on salt reduction. Conclusions: There is a strong education gradient in HBP awareness, treatment and control as well as salt knowledge and perceived intake. Enhancements in public and patient knowledge and awareness of HBP and its risk factors targeting socio-economically disadvantaged groups are urgently needed to alleviate the growing HBP burden in low- and middle-income countries. [ABSTRACT FROM AUTHOR]

Objective: The World Health Organization (WHO) recommends that adults consume less than 5 grams of salt per day to reduce the risk of cardiovascular disease. This study aims to examine the average population daily salt intake in the 53 Member States of the WHO European Region.Design: A systematic review was conducted to examine the most up-to-date salt intake data for adults published between 2000 and 2022. Data were obtained from peer-reviewed and grey literature, WHO surveys and studies, as well as from national and global experts.Setting: The 53 Member States of the WHO European Region.Participants: People aged 12 years or more.Results: We identified 50 studies published between 2010-2021. Most countries in the WHO European Region (n = 52, 98%) reported salt intake above WHO recommended maximum levels. In almost all countries (n = 52, 98%), men consume more salt than women, ranging between 5.39 - 18.51g for men and 4.27 - 16.14g for women. Generally, Western and Northern European countries have the lowest average salt intake, whilst Eastern European and Central Asian countries have the highest average. 42% of the fifty-three countries (n = 22) measured salt intake using 24h urinary collections, considered the gold standard method.Conclusions: This study found that salt intakes in the WHO European Region are significantly above WHO recommended levels. Most Member States of the Region have conducted some form of population salt intake. However, methodologies to estimate salt intake are highly disparate and underestimations are very likely. [ABSTRACT FROM AUTHOR]

It is unclear if Nosocomial Spontaneous Bacteria Peritonitis (NSBP) is associated with higher mortality compared with community acquired spontaneous bacterial peritonitis. Database search from inception to May 2022 was conducted. The databases included MEDLINE, EMBASE, Cochrane registry of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus. Inclusion criteria were as follows: adult patients, age >18 years, with a diagnosis of NSBP. Pooled estimates of mortality were calculated following the restricted maximum likelihood method. The mortality rate between NSBP and CA-SBP was reported as odds ratio (OR) and 95% confidence interval (CI). Data synthesis was obtained using random effects meta-analysis. Heterogeneity was reported as I2. A total of 482 unique titles were screened. Twenty-two articles were included. A total of 2,145 patients with NSBP were included. Patients were followed for a median of 90 days. The pooled mortality rate of NSBP was 52.51% (95% CI 42.77–62.06%; I2 83.72%). Seven studies compared the mortality outcome of patients with NSBP and CA-SBP. NSBP was significantly associated with a higher rate of mortality (OR 2.78, 95% CI 1.87–4.11; I2 36.00%). NSBP was associated with higher mortality rate compared to CA-SBP, which could be due to a higher rate of resistance organisms. [ABSTRACT FROM AUTHOR]

Antiretroviral therapy (ART) significantly reduced Human Immunodeficiency Virus (HIV) morbidity and mortality; nevertheless, stigma still characterises the living with this condition. This study explored patients' coping experience by integrating narrative medicine (NM) in a non-interventional clinical trial. From June 2018 to September 2020 the study involved 18 centres across Italy; enrolled patients were both D/C/F/TAF naïve and previously ART-treated. Narratives were collected at enrolment (V1) and last visit (V4) and then independently analysed by three NM specialist researchers through content analysis. One-hundred and fourteen patients completed both V1 and V4 narratives. Supportive relationships with clinicians and undetectable viral load facilitated coping. Conversely, lack of disclosure of HIV-positive status, HIV metaphors, and unwillingness to narrate the life before the diagnosis indicated internalised stigma. This is the first non-interventional study to include narratives as patient reported outcomes (PROs). Improving HIV awareness and reducing the sense of guilt experienced by patients helps to overcome stigma and foster coping. [ABSTRACT FROM AUTHOR]

Biallelic KARS1 mutations cause KARS-related diseases, a rare syndromic condition encompassing central and peripheral nervous system impairment, heart and liver disease, and deafness. KARS1 encodes the t-RNA synthase of lysine, an aminoacyl-tRNA synthetase, involved in different physiological mechanisms (such as angiogenesis, post-translational modifications, translation initiation, autophagy and mitochondrial function). Although patients with immune-hematological abnormalities have been individually described, results have not been collectively discussed and functional studies investigating how KARS1 mutations affect B cells have not been performed. Here, we describe one patient with severe developmental delay, sensoneurinal deafness, acute disseminated encephalomyelitis, hypogammaglobulinemia and recurrent infections. Pathogenic biallelic KARS1 variants (Phe291Val/ Pro499Leu) were associated with impaired B cell metabolism (decreased mitochondrial numbers and activity). All published cases of KARS-related diseases were identified. The corresponding authors and researchers involved in the diagnosis of inborn errors of immunity or genetic syndromes were contacted to obtain up-to-date clinical and immunological information. Seventeen patients with KARS-related diseases were identified. Recurrent/severe infections (9/17) and B cell abnormalities (either B cell lymphopenia [3/9], hypogammaglobulinemia [either IgG, IgA or IgM; 6/15] or impaired vaccine responses [4/7]) were frequently reported. Immunoglobulin replacement therapy was given in five patients. Full immunological assessment is warranted in these patients, who may require detailed investigation and specific supportive treatment. [ABSTRACT FROM AUTHOR]

Inspiratory muscle training (IMT) has been used in different sports, although there is no consensus on its benefits. We investigated the effects of eight weeks of IMT in women's handball. Twenty-four players were randomly distributed into experimental (EXP; n = 13) and control (CON; n = 11) groups. Only the EXP group performed IMT using the POWERBreathe device, following indications of the manufacturers. Before and after the intervention, spirometric variables were evaluated at rest and during a graded test using direct analysis of respiratory gases. Perception of exertion at submaximal intensity was also determined. No significant differences were observed post- vs. pre-intervention (p ≥ 0.05) regarding forced vital capacity (FVC), forced expiratory volume in the 1st second (VEF1), FVC/VEF1, maximal expiratory flow at 50% of FVC or peak inspiratory flow. Post-intervention, only the CON group increased their absolute and relative VO2max (2.1 ± 0.2 L/min pre vs. 2.2 ± 0.3 L/min post; 33.6 ± 3.6 ml/kg·min pre vs. 34.5 ± 3.2 ml/kg·min post, respectively). No significant improvements (p ≥ 0.05) were observed in VO2 associated with ventilatory threshold 1 (VT1), nor in the intensity associated with VO2max and VT1. However, there was a tendency for the mentioned variables to decrease in the CON group, while in the EXP group the trend was to maintain or increase previous values. IMT did not determine an improvement in the perception of exertion at submaximal intensity. The use of POWERBreathe, as described in the present study, is feasible in terms of time and effort, although its benefits may not be significant. [ABSTRACT FROM AUTHOR]

The association between salt-related knowledge, attitude, behaviour (KAB) and actual salt consumption in Greek adults is uncertain. This study investigates the correlation between salt intake, gauged by 24-h urinary sodium excretion, with salt-related KAB. It further explores how socio-demographic factors influence these behaviors. Salt consumption was evaluated using a 24-h urinary sodium test, and compared to self-reported KAB data. Knowledge and behavior scores related to salt were computed. An overall cohort-adjusted model examined the relationship between daily salt consumption, knowledge and behavior scores, and certain covariates. Through the stratification by the cohort random effect, two models were established (Cohort I Adults; Cohort II Students) examining the same relationships of the overall cohort model. 463 Greek adults participated. The average salt intake was 9.54 g/day, nearly double the WHO recommendation. Significant differences in knowledge scores were noted based on sex, age, education, and BMI. A trend suggesting lower discretionary salt use with increased salt intake was observed (p = 0.06). However, comprehensive analysis revealed no direct correlation between salt intake and either knowledge (p = 0.562) or behavior scores (p = 0.210). The results emphasize the need for food product reforms by industry stakeholders and accelerated efforts towards reducing salt intake. [ABSTRACT FROM AUTHOR]

Skilful expertise is grounded in practical, performative knowledge-how, not in detached, spectatorial knowledge-that, and knowledge-how is embodied by habitual dispositions, not representation of facts and rules. Consequently, as action control is a key requirement for the intelligent selection, initiation, and regulation of skilful performance, habitual action control, i.e. the kind of action control based on habitual dispositions, is the true hallmark of skill and the only veridical criterion to evaluate expertise. Not only does this imply that knowledge-that does not make your actions more skilful, but it also implies that it makes them less skilful. This thesis, that I call Radical Habitualism, finds a precursor in Hubert Dreyfus. His approach is considered extreme by most philosophers of skill & expertise: an agent –says Dreyfus– does not perform like an expert when they lack the embodied dispositions necessary to control their action habitually or when they stop relying on such dispositions to control their actions. Thus, one cannot perform skilfully if their actions are guided by representations (isomorphic schemas, explicit rules, and contentful instructions), as the know-that that they convey disrupts or diminishes the agent’s habitual engagement with the task at hand. In defence of Radical Habitualism, I will argue that only the contentless know-how embedded in habitual dispositions fulfils (i) the genetic, (ii) the normative, and (iii) the epistemic requirements of skilful performance. I will examine the phenomenological premises supporting Dreyfus’ approach, clarify their significance for a satisfactory normative and explanatory account of skilful expertise, and rebut the most common objections raised by both intellectualists and conciliatory habitualists, concerning hybrid actions guided by a mix of habitual and representational forms of control. In revisiting Dreyfus anti-representationalist approach, I will particularly focus on its epistemological implications, de-emphasizing other considerations related to conscious awareness. [ABSTRACT FROM AUTHOR]

The clinical and economic burden of hypertension is high and continues to increase globally. Uncontrolled hypertension has severe but avoidable long‐term consequences, including cardiovascular diseases, which are among the most burdensome and most preventable conditions in Europe. Yet, despite clear guidelines on screening, diagnosis and management of hypertension, a large proportion of patients remain undiagnosed or undertreated. Low adherence and persistence are common, exacerbating the issue of poor blood pressure (BP) control. Although current guidelines provide clear direction, implementation is hampered by barriers at the patient‐, physician‐ and healthcare system levels. Underestimation of the impact of uncontrolled hypertension and limited health literacy lead to low adherence and persistence among patients, treatment inertia among physicians and a lack of decisive healthcare system action. Many options to improve BP control are available or under investigation. Patients would benefit from targeted health education, improved BP measurement, individualized treatment or simplified treatment regimens through single‐pill combinations. For physicians, increasing awareness of the burden of hypertension, as well as offering training on monitoring and optimal management and provision of the necessary time to collaboratively engage with patients would be useful. Healthcare systems should establish nationwide strategies for hypertension screening and management. Furthermore, there is an unmet need to implement more comprehensive BP measurements to optimize management. In conclusion, an integrative, patient‐focused, multimodal multidisciplinary approach to the management of hypertension by clinicians, payers and policymakers, involving patients, is required to achieve long‐term improvements in population health and cost‐efficiency for healthcare systems. [ABSTRACT FROM AUTHOR]

POU3F3 variants cause developmental delay, behavioral problems, hypotonia and dysmorphic features. We investigated the phenotypic and genetic landscape, and genotype–phenotype correlations in individuals with POU3F3‐related disorders. We recruited unpublished individuals with POU3F3 variants through international collaborations and obtained updated clinical data on previously published individuals. Trio exome sequencing or single exome sequencing followed by segregation analysis were performed in the novel cohort. Functional effects of missense variants were investigated with 3D protein modeling. We included 28 individuals (5 previously published) from 26 families carrying POU3F3 variants; 23 de novo and one inherited from an affected parent. Median age at study inclusion was 7.4 years. All had developmental delay mainly affecting speech, behavioral difficulties, psychiatric comorbidities and dysmorphisms. Additional features included gastrointestinal comorbidities, hearing loss, ophthalmological anomalies, epilepsy, sleep disturbances and joint hypermobility. Autism, hearing and eye comorbidities, dysmorphisms were more common in individuals with truncating variants, whereas epilepsy was only associated with missense variants. In silico structural modeling predicted that all (likely) pathogenic variants destabilize the DNA‐binding region of POU3F3. Our study refined the phenotypic and genetic landscape of POU3F3‐related disorders, it reports the functional properties of the identified pathogenic variants, and delineates some genotype–phenotype correlations. [ABSTRACT FROM AUTHOR]

Aims: Comorbidities play a significant role towards the pathophysiology of heart failure with preserved ejection fraction (HFpEF), characterized by abnormal macrovascular function and altered ventricular–vascular coupling. However, our understanding of the role of comorbidities and arterial stiffness in HFpEF remains incomplete. We hypothesized that HFpEF is preceded by a cumulative rise in arterial stiffness as cardiovascular comorbidities accumulate, beyond that associated with ageing. Methods and results: Arterial stiffness was assessed using pulse wave velocity (PWV) in five groups: Group A, healthy volunteers (n = 21); Group B, patients with hypertension (n = 21); Group C, hypertension and diabetes mellitus (n = 20); Group D, HFpEF (n = 21); and Group E, HF with reduced ejection fraction (HFrEF) (n = 11). All patients were aged 70 and above. Mean PWV increased from Groups A to D (PWV 10.2, 12.2, 13.0, and 13.7 m/s, respectively) as vascular comorbidities accumulated independent of age, renal function, haemoglobin, obesity (body mass index), smoking status, and hypercholesterolaemia. HFpEF exhibited the highest PWV and HFrEF displayed near‐normal levels (13.7 vs. 10 m/s, P = 0.003). PWV was inversely related to peak oxygen consumption (r = −0.304, P = 0.03) and positively correlated with left ventricular filling pressures (E/e′) on echocardiography (r = −0.307, P = 0.014). Conclusions: This study adds further support to the concept of HFpEF as a disease of the vasculature, underlined by an increasing arterial stiffness that is driven by vascular ageing and accumulating vascular comorbidities, for example, hypertension and diabetes. Reflecting a pulsatile arterial afterload associated with diastolic dysfunction and exercise capacity, PWV may provide a clinically relevant tool to identify at‐risk intermediate phenotypes (e.g. pre‐HFpEF) before overt HFpEF occurs. [ABSTRACT FROM AUTHOR]

Background: The gastroesophageal reflux disease (GERD) worldwide prevalence is increasing maybe due to population aging and the obesity epidemic. Nissen fundoplication is the most common surgical procedure for GERD with a failure rate of approximately 20% which might require a redo surgery. The aim of this study was to evaluate the short- and long-term outcomes of robotic redo procedures after anti-reflux surgery failure including a narrative review. Methods: We reviewed our 15-year experience from 2005 to 2020 including 317 procedures, 306 for primary, and 11 for revisional surgery. Results: Patients included in the redo series underwent primary Nissen fundoplication with a mean age of 57.6 years (range, 43–71). All procedures were minimally invasive and no conversion to open surgery was registered. The meshes were used in five (45.45%) patients. The mean operative time was 147 min (range, 110–225) and the mean hospital stay was 3.2 days (range, 2–7). At a mean follow-up of 78 months (range, 18–192), one patient suffered for persistent dysphagia and one for delayed gastric emptying. We had two (18.19%) Clavien–Dindo grade IIIa complications, consisting of postoperative pneumothoraxes treated with chest drainage. Conclusion: Redo anti-reflux surgery is indicated in selected patients and the robotic approach is safe when it is performed in specialized centers, considering its surgical technical difficulty. [ABSTRACT FROM AUTHOR]

Background: Aujeszky's disease is mainly a swine disease, still endemic worldwide. It can infect other mammalians, including human beings, and it is usually fatal with nervous symptoms. Ever since the disease was detected in 1988 in Argentina, many outbreaks have been reported involving both feral swine and dogs. Aim: At present, in Argentina, Pseudorabies virus (PRV) cases are sporadically reported; however, clinical cases are informed. This study aims to obtain information about the seroprevalence of PRV in wild boars and to isolate and characterize PRV from clinical samples. Methods: From 2018 to 2019, 78 wild boars' serum samples from Bahía de Samborombón natural reserve were analyzed for antibodies to PRV using a virus neutralization test. Clinical samples from 17 pigs, 2 wild boars, 1 dog, and 1 cat were collected from 2013 to 2019 for viral isolation and detection of the presence of the gD gene by PCR. For sequence analysis, the gC partial gene was amplified. Results: Five strains were isolated from the dog, cat, and swine samples. The new PRV strains identified were confirmed by BLAST analysis, which revealed between 99.74% and 100% of similarity to the NIA-3 strain and phylogenetic analysis of the partial gene encoding the gC protein revealed that the PRV strains have divided into two main clades, clade 1 and clade 2. Conclusion: This report informed that most new cases of PRV were detected in the central regions of Argentina, where pig production is concentrated. The study in Bahía de Samborombón revealed a high percentage of detection but, the sampling is not representative of that of the rest of the country. Therefore, a systematic sampling effort of wild boar throughout the country should be included in the national program control. Although in Argentina only the inactivated Bartha vaccine is allowed, recombination risk should not be ignored if attenuated vaccines are incorporated into the National control plan. The two strains, one from the cat and one from the dog sample, are directly related to infected swine. The information about clinical cases and molecular characterization of new strains is important for a better understanding of the dynamics of PRV and to promote preventive measures. [ABSTRACT FROM AUTHOR]

Introduction: Approximately a third of cancer-related deaths are attributable to modifiable factors. Methods: As a pilot experience, a cross-sectional survey was conducted in 8,000 citizens residing in four different municipalities of the Salerno province (Sarno, Pagani, San Valentino Torio, and San Marzano sul Sarno) to investigate key lifestyle and dietary habits. Results: A total of 703 of participants (8.7%) reported a history of malignancy. Alarmingly, 30.5% declared to be a current smoker, while 78.8% did not report any kind of physical activity. Encouragingly, 64.5% declared to be abstemious, and 83.0% declared to consume fruit and vegetables every day, while 4.7% and 31.9% declared not to consume meat and fried food, respectively, at any time. Never-consumers of fruit and vegetables had higher odds of having a history of colorectal cancer (OR = 5.01; 95% CI = 1.46–17.15; p = 0.01). Conclusions: The PREVES study has served to prove the validity of an operational model allowing to integrate hospital and territorial healthcare services, which we expect to be applied at a larger scale. Key information regarding dietary and lifestyle habits of the investigated population was obtained. Larger studies conducted using more accurate approaches to investigate diet, such as 24-h recalls and food frequency questionnaires, are warranted. [ABSTRACT FROM AUTHOR]

DNA methylation comprises a cumulative record of lifetime exposures superimposed on genetically determined markers. Little is known about methylation dynamics in humans following an acute perturbation, such as infection. We characterized the temporal trajectory of blood epigenetic remodeling in 133 participants in a prospective study of young adults before, during, and after asymptomatic and mildly symptomatic SARS‐CoV‐2 infection. The differential methylation caused by asymptomatic or mildly symptomatic infections was indistinguishable. While differential gene expression largely returned to baseline levels after the virus became undetectable, some differentially methylated sites persisted for months of follow‐up, with a pattern resembling autoimmune or inflammatory disease. We leveraged these responses to construct methylation‐based machine learning models that distinguished samples from pre‐, during‐, and postinfection time periods, and quantitatively predicted the time since infection. The clinical trajectory in the young adults and in a diverse cohort with more severe outcomes was predicted by the similarity of methylation before or early after SARS‐CoV‐2 infection to the model‐defined postinfection state. Unlike the phenomenon of trained immunity, the postacute SARS‐CoV‐2 epigenetic landscape we identify is antiprotective. Synopsis: Characterization of the temporal dynamics of blood methylation changes in young adults following asymptomatic and mild SARS‐CoV‐2 infection brings insights into the long‐term memory of environmental exposure and potential disease associations.Both symptomatic and asymptomatic infections induce methylation changes that are not always associated with gene expression changes.Methylation changes persist for longer than gene expression changes.The complex dynamics of methylation alterations can be used to predict the timing of infection.Contrary to the trained immunity phenomenon, the presence of a post‐infection‐like methylation state at baseline is anti‐protective for subsequent SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]

The short pre-M1 helix within the S1–M1 linker (also referred to as the pre-M1 linker) between the agonist-binding domain (ABD, S1) and the M1 transmembrane helix of the NMDA receptor (NMDAR) is devoid of missense variants within the healthy population but is a locus for de novo pathogenic variants associated with neurological disorders. Several de novo variants within this helix have been identified in patients presenting early in life with intellectual disability, developmental delay, and/or epilepsy. In this study, we evaluated functional properties for twenty variants within the pre-M1 linker in GRIN1, GRIN2A, and GRIN2B genes, including six novel missense variants. The effects of pre-M1 variants on agonist potency, sensitivity to endogenous allosteric modulators, response time course, channel open probability, and surface expression were assessed. Our data indicated that virtually all of the variants evaluated altered channel function, and multiple variants had profound functional consequences, which may contribute to the neurological conditions in the patients harboring the variants in this region. These data strongly suggest that the residues within the pre-M1 helix play a key role in channel gating and are highly intolerant to genetic variation. [ABSTRACT FROM AUTHOR]