Peripheral neuropathy in patients with gout, beyond focal nerve compression: a cross-sectional study.

Neuropathies secondary to tophus compression in gout patients are well known; however, limited data exist on other types of peripheral neuropathies (PN). Our aim was to describe PN frequency, characteristics, distribution, patterns, and associated factors in gout patients through clinical evaluation, a PN questionnaire, and nerve conduction studies (NCS). This cross-sectional descriptive study included consecutive gout patients (ACR/EULAR 2015 criteria) from our clinic. All underwent evaluation by Rheumatology and Rehabilitation departments, with IRB approval. Based on NCS, patients were categorized as PN + (presence) or PN- (absence). PN + patients were further classified as local peripheral neuropathy (LPN) or generalized somatic peripheral neuropathy (GPN). We enrolled 162 patients, 98% male (72% tophaceous gout). Mean age (SD): 49.4 (12) years; mean BMI: 27.9 (6.0) kg/m2. Comorbidities included dyslipidemia (53%), hypertension (28%), and obesity (23.5%). Abnormal NCS: 65% (n = 106); 52% LPN, 48% GPN. PN + patients were older, had lower education, and severe tophaceous gout. GPN patients were older, had lower education, and higher DN4 scores compared to LPN or PN- groups (p = 0.05); other risk factors were not significant. Over half of gout patients experienced neuropathy, with 48% having multiplex mononeuropathy or polyneuropathy. This was associated with joint damage and functional impairment. Mechanisms and risk factors remain unclear. Early recognition and management are crucial for optimizing clinical outcomes and quality of life in these patients. Key Points Peripheral neuropathies in gout patients had been scarcely reported and studied. This paper report that: • PN in gout is more frequent and more diverse than previously reported. • Mononeuropathies are frequent, median but also ulnar, peroneal and tibial nerves could be injured. • Unexpected, generalized neuropathies (polyneuropathy and multiplex mononeuropathy) are frequent and associated to severe gout. • The direct role of hyperuricemia /or gout in peripheral nerves require further studies.

Nurses' perceptions of the performance of nurse managers and senior hospital management during the COVID-19 pandemic.

BACKGROUND: The first waves of the COVID-19 pandemic had a negative impact on health systems and health professionals, due to the high number of cases and a lack of preparation. The aim of this study was to understand how nurses working in hospital units and in intensive care perceived the performance of nurse managers and senior hospital management during the first two waves of the pandemic. METHODS: The phenomenological approach proposed by Giorgi was used to investigate perceptions of the performance of nurse managers and senior hospital management during the first two waves of the COVID-19 pandemic in Spain. Fourteen clinical nurses who worked on the front line in inpatient units or intensive care units of the Health Services of Extremadura and Madrid in the first (March-April 2020) and second (October-November 2020) waves of the COVID-19 pandemic participated in this study. The data was collected through semi-structured interviews, following a script of themes, in a theoretical sample of nurses who were worked during the pandemic. RESULTS: Two main themes emerged from the analysis of the data: (1) perceptions about the performance of nurse managers and senior hospital managers during the first and second waves of the pandemic (health system failure; belief that senior hospital management professionals could have managed the pandemic better; recognizing the efforts of middle management (nursing supervisors); insufficient institutional support) and (2) strategies employed by nurses to compensate for the weaknesses in pandemic management. CONCLUSIONS: The clinical nurses perceived that the nurse managers demonstrated better management of the pandemic than the hospital's senior management, which they attribute to their proximity, empathy, accessibility, and ability to mediate between them and the senior management. The nurses also believe that the senior management of the hospitals was to blame for organisational failures and the poor management of the pandemic.

A wound-induced differentiation trajectory for neurons.

Animals capable of whole-body regeneration can replace any missing cell type and regenerate fully functional new organs, including new brains, de novo. The regeneration of a new brain requires the formation of diverse neural cell types and their assembly into an organized structure with correctly wired circuits. Recent work in various regenerative animals has revealed transcriptional programs required for the differentiation of distinct neural subpopulations, however, how these transcriptional programs are initiated in response to injury remains unknown. Here, we focused on the highly regenerative acoel worm, Hofstenia miamia, to study wound-induced transcriptional regulatory events that lead to the production of neurons and subsequently a functional brain. Footprinting analysis using chromatin accessibility data on a chromosome-scale genome assembly revealed that binding sites for the Nuclear Factor Y (NFY) transcription factor complex were significantly bound during regeneration, showing a dynamic increase in binding within one hour upon amputation specifically in tail fragments, which will regenerate a new brain. Strikingly, NFY targets were highly enriched for genes with neuronal function. Single-cell transcriptome analysis combined with functional studies identified soxC+ stem cells as a putative progenitor population for multiple neural subtypes. Further, we found that wound-induced soxC expression is likely under direct transcriptional control by NFY, uncovering a mechanism for the initiation of a neural differentiation pathway by early wound-induced binding of a transcriptional regulator.

ENERGY EXPENDITURE OF INTERNATIONAL FEMALE RUGBY UNION PLAYERS DURING A MAJOR INTERNATIONAL TOURNAMENT: A DOUBLY LABELLED WATER STUDY.

The purpose of this study was to quantify the total energy expenditure (TEE) of international female rugby union players. Fifteen players were assessed over 14-days throughout an international multi-game tournament, which represented two consecutive one-match microcycles. Resting metabolic rate (RMR) and TEE were assessed by indirect calorimetry and doubly labelled water, respectively. Physical activity level (PAL) was estimated (TEE:RMR). Mean RMR, TEE, and PAL were 6.60 ± 0.93 MJ.day-1, 13.51 ± 2.28 MJ.day-1 and 2.0 ± 0.3 AU, respectively. There was no difference in TEE (13.74 ± 2.31 vs. 13.92 ± 2.10 MJ.day-1; p = 0.754), or PAL (2.06 ± 0.26 AU vs. 2.09 ± 0.23 AU; p = 0.735) across microcycles, despite substantial decreases in training load (total distance: -8088 m, collisions: -20 n, training duration: -252 min). After correcting for body composition, there was no difference in TEE (13.80 ± 1.74 vs. 13.16 ± 1.97 adj. MJ.day-1, p = 0.190), RMR (6.49 ± 0.81 vs. 6.73 ± 0.83 adj. MJ.day-1, p = 0.633) or PAL (2.15 ± 0.14 vs 1.87 ± 0.26 AU, p = 0.090) between forwards and backs. For an injured participant (n = 1), TEE reduced by 1.7 MJ.day-1 from pre-injury. For participants with illness (n = 3), TEE was similar to pre-illness (+0.49 MJ.day-1). The energy requirements of international female rugby players were consistent across one-match microcycles. Forwards and backs had similar adjusted energy requirements. These findings are critical to inform the dietary guidance provided to female rugby players.

Implementation of Society for Cardiovascular Angiography and Interventions classification in patients with cardiogenic shock secondary to acute myocardial infarction in a spanish university hospital.

BACKGROUND: Killip-Kimball classification has been used for estimating death risk in patients suffering acute myocardial infarction (AMI). Killip-Kimball stage IV corresponds to cardiogenic shock. However, the Society for Cardiovascular Angiography and Interventions (SCAI) classification provides a more precise tool to classify patients according to shock severity. The aim of this study was to apply this classification to a cohort of Killip IV patients and to analyze the differences in death risk estimation between the two classifications. METHODS: A single-center retrospective cohort study of 100 consecutive patients hospitalized for "Killip IV AMI" between 2016 and 2023 was performed to reclassify patients according to SCAI stage. RESULTS: Distribution of patients according to SCAI stages was B=4%, C=53%, D=27%, E=16%. Thirty-day mortality increased progressively according to these stages (B=0%, C=11.88%, D=55.56%, E=87.50%; P<0.001). The exclusive use of Killip IV stage overestimated death risk compared to SCAI C (35% vs. 11.88%, P=0.002) and underestimated it compared to SCAI D and E stages (35% vs. 55.56% and 87.50%, P=0.03 and P<0.001, respectively). Age >69 years, creatinine >1.15 mg/dl and advanced SCAI stages (SCAI D and E) were independent predictors of 30-day mortality. Mechanical circulatory support use showed an almost significant benefit in advanced SCAI stages (D and E hazard ratio, 0.45; 95% confidence interval, 0.19-1.06; P=0.058). CONCLUSIONS: SCAI classification showed superior death risk estimation compared to Killip IV. Age, creatinine levels and advanced SCAI stages were independent predictors of 30-day mortality. Mechanical circulatory support could play a beneficial role in advanced SCAI stages.

Colonic Metastasis in a Patient With Hereditary Diffuse Gastric Cancer: A Case Report.

Metastasis of gastric carcinoma to atypical locations can complicate management, often leading clinicians to rely heavily on chemotherapy. While instances of gastric carcinoma spreading to the liver, peritoneum, and lymphatics are well documented in the literature, there is limited evidence of its spread to intraintestinal organs, particularly the colon. This scarcity of reports complicates diagnosis, given the variations in histopathology. This case report highlights a 35-year-old patient diagnosed with colonic metastasis from hereditary diffuse gastric cancer (HDGC) while being evaluated for potential causes of iron deficiency anemia. A mutation in the E-cadherin (CDH1) tumor suppressor gene is associated with HDGC. Dysregulation of CDH1 leads to tumor proliferation, invasion, migration, and metastasis. Treatment options for gastric cancer include surgical resection with neoadjuvant or adjuvant chemotherapy or palliative care with chemotherapy in metastatic disease. Although colonic metastasis from gastric cancer is rare, documented incidents can offer valuable insights that avoid misdiagnosing primary tumors and help guide further management.

Acute effects on the psychological perception of university students after participation in the "RegulACTION" workshop for the improvement of emotional health and promotion of an active lifestyle.

Introduction: Prospective research in Health Sciences and Sports Sciences warns of the need to design and implement educational program at the different stages of human development, that promote emotional competences, interpersonal competences, an adequate level of healthy physical activity as well as adherence to the Mediterranean diet and a more active lifestyle on a physical and social level. The main objective of the study was to design an intervention program on intra-and interpersonal competences together with emotional education, nutritional education and healthy physical activity, called 'RegulACTION'. Methods: The preliminary study sample consisted of 11 participants aged 21-28 years (M = 5.00, SD = 8.76) (8 female and 3 males) university students. An ad hoc questionnaire was elaborated to evaluate the participant's perception of the usefulness of the 'RegulACTION' experience and a semi-structured interview of 5 questions to assess their perception, identification of their emotions, awareness of their cognitions, emotions and behaviors in the different areas of their lives. Results: The descriptive results show that the participants are receptive to continuing training in the regulation of cognitions (thoughts) and emotions to increase their satisfaction in different areas of their lives. Regarding the qualitative results, the participants' perception, collected verbatim, is that they feel the need to apply the knowledge about personal and social emotions, as well as healthy behavior in terms of nutrition and exercise, in their daily lives. Discussion: The 'RegulACTION' program is designed based on the assessment of the prevalence of mental illness in the young adult and adult population, in line with the literature review in the area of knowledge of the theory of emotions, motivational theories and on the occasion of the development of a workshop organized.

Validity, reliability, and the contributing physical characteristics of a modified 15m prone Yo-Yo Intermittent Recovery Test Level-1 test in elite female rugby league players.

This study aims to establish the validity and reliability of the prone Yo-YoIRL1 in elite female rugby league players (part one) and determine the anthropometric and physical characteristics contributing to 15m prone Yo-YoIRL1 performance (part two). Part one, 21 subjects completed one Yo-YoIRL1, one 20m and two 15m prone Yo-YoIRL1 tests over four sessions, with 7-14 days in-between. Part two, ten subjects completed a testing battery, including body mass, height, dual-energy x-ray absorptiometry, isometric mid-thigh pull, isometric bench-press, 10m and 20m sprints and an incremental treadmill test ([Formula: see text]). The 15m prone YoYoIRL1 demonstrated poor reliability with a typical error of 68m (21%) and a smallest worthwhile change of 54m (9%). Validity analysis found the prone versions of the YoYoIRL1 were not sensitive measures of intermittent running performance. Both prone YoYoIRL1 test distances demonstrated large mean bias (76% and -37% respectively) and typical error of the estimate (19% and 21%, respectively) in comparison to the YoYoIRL1. Body mass (r = -0.89), lean mass (r = -0.64), body fat % (r = -0.68), [Formula: see text] (l∙min-1) (r = -0.64), IMTP (r = -0.69), IBP (r = -0.15), 10m (r = -0.77) and 20m (r = -0.72) momentum displayed large negative relationships with 15m prone Yo-YoIRL1 performance. Due to the poor validity of the 20m prone YoYoIRL1, the poor validity and reliability of the 15m prone YoYoIRL1, and the anthropometric and physical characteristics which negatively impact performance, practitioners should reconsider the use of the prone YoYoIRL1 test to monitor high intensity intermittent running performance.

Data-Driven Modeling of the Spray Drying Process. Process Monitoring and Prediction of the Particle Size in Pharmaceutical Production.

Spray drying is used in the pharmaceutical industry for particle engineering of amorphous solid dispersions (ASDs). The particle size of the spray-dried (SD) powders is one of their key attributes due to its impact on the downstream processes and the drug product's functional properties. Offline and inline laser diffraction methods can be used to estimate the product's particle size; however, the final release of these ASDs is based on offline instruments. This paper presents a novel data-driven modeling approach for predicting the particle size of SD products. The model-based characterization of the process and the product's particle size, as a critical quality attribute, follows the quality by design principles. The resulting model can be used for online process monitoring, reducing the risks of out-of-specifications products and supporting their real-time release. A Tucker3 model is trained to capture and factorize the deterministic variability of the process. Subsequently, a partial least-squares regression model is calibrated to model the impact that variability in the input material properties, the process parameters, and the spray nozzle have on the products' particle size. This strategy has been calibrated and validated using large scale production data for two intermediate drug products under high sparsity of particle size data. Despite the challenges, high accuracy was obtained in predicting the median particle size (dv50) for release. The 99% confidence interval results in an error of maximum 2.5 µm, which is less than 10% of the allowed range of variation.

Exploring Genetic Silencing: RNAi and CRISPR-Cas Potential Against Drug Resistance in Malaria.

Malaria has been one of the most lethal infectious diseases throughout history, claiming a high number of human lives. The genomic plasticity of Plasmodium falciparum, the causative agent of the most severe and deadly form of malaria, gives the parasite a constant resistance to drugs developed for its control. Despite efforts to control and even eradicate the disease, these have largely been unsuccessful due to the parasite's continuous adaptations. This study aims to examine the key genes involved in parasite resistance and propose a shift in the combat strategy. Gene silencing techniques offer promise in combating malaria, yet further research is needed to harness their potential for disease control fully. Although there is still a long way to go for the implementation of gene silencing-based therapeutic strategies, this review addresses examples of the use of such techniques in various human diseases and how they could be extrapolated for malaria treatment.

TATA-Binding Protein-Based Virtual Screening of FDA Drugs Identified New Anti-Giardiasis Agents.

Parasitic diseases, predominantly prevalent in developing countries, are increasingly spreading to high-income nations due to shifting migration patterns. The World Health Organization (WHO) estimates approximately 300 million annual cases of giardiasis. The emergence of drug resistance and associated side effects necessitates urgent research to address this growing health concern. In this study, we evaluated over eleven thousand pharmacological compounds sourced from the FDA database to assess their impact on the TATA-binding protein (TBP) of the early diverging protist Giardia lamblia, which holds medical significance. We identified a selection of potential pharmacological compounds for combating this parasitic disease through in silico analysis, employing molecular modeling techniques such as homology modeling, molecular docking, and molecular dynamics simulations. Notably, our findings highlight compounds DB07352 and DB08399 as promising candidates for inhibiting the TBP of Giardia lamblia. Also, these compounds and DB15584 demonstrated high efficacy against trophozoites in vitro. In summary, this study identifies compounds with the potential to combat giardiasis, offering the prospect of specific therapies and providing a robust foundation for future research.

Unveiling the Structural Properties, Optical Behavior, and Thermoelectric Performance of 2D CsSn2Br5 Halide Obtained by Mechanochemistry.

Metal halide perovskites with a two-dimensional structure are utilized in photovoltaics and optoelectronics. High-crystallinity CsSn2Br5 specimens have been synthesized via ball milling. Differential scanning calorimetry curves show melting at 553 K (endothermic) and recrystallization at 516 K (exothermic). Structural analysis using synchrotron X-ray diffraction data, collected from 100 to 373 K, allows for the determination of Debye model parameters. This analysis provides insights into the relative Cs-Br and Sn-Br chemical bonds within the tetragonal structure (space group: I4/mcm), which remains stable throughout the temperature range studied. Combined with neutron data, X-N techniques permit the identification of the Sn2+ lone electron pair (5s2) in the two-dimensional framework, occupying empty space opposite to the four Sn-Br bonds of the pyramidal [SnBr4] coordination polyhedra. Additionally, diffuse reflectance UV-vis spectroscopy unveils an indirect optical gap of approximately ∼3.3 eV, aligning with the calculated value from the B3LYP-DFT method (∼3.2 eV). The material exhibits a positive Seebeck coefficient as high as 6.5 × 104 µV K-1 at 350 K, which evolves down to negative values of -3.0 × 103 µV K-1 at 550 K, surpassing values reported for other halide perovskites. Notably, the thermal conductivity remains exceptionally low, between 0.32 and 0.25 W m-1 K-1.

Cancer Core Europe: Leveraging Institutional Synergies to Advance Oncology Research and Care Globally.

Cancer Core Europe brings together the expertise, resources, and interests of seven leading cancer institutes committed to leveraging collective innovation and collaboration in precision oncology. Through targeted efforts addressing key medical challenges in cancer and partnerships with multiple stakeholders, the consortium seeks to advance cancer research and enhance equitable patient care.

Direct Access to Benzolactams and Benzolactones via Nickel Catalyzed Carbonylation with CO2.

A new nickel catalyzed cross-electrophile coupling for accessing γ-lactams (isoindolinones) as well as γ-lactones (isobenzofuranones) via carbonylation with CO2 is documented. The protocol exploits the synergistic role of redox-active Ni(II) complexes and AlCl3 as a CO2 activator/oxygen scavenger, leading to the formation of a wide range of cyclic amides and esters (28 examples) in good to high yields (up to 87%). A dedicated computational investigation revealed the multiple roles played by AlCl3. In particular, the simultaneous transient protection of the pendant amino group of the starting reagents and the formation of the electrophilically activated CO2-AlCl3 adduct are shown to concur in paving the way for an energetically favorable mechanistic pathway.

Exploring risk factors of severe pituitary apoplexy: Insights from a multicenter study of 71 cases.

PURPOSE: To identify clinical and radiological factors associated with a higher risk of developing a severe pituitary apoplexy (PA). METHODS: Multicenter retrospective study of patients presenting with clinical PA in three Spanish tertiary hospitals of Madrid between 2008 and 2022. We classified PA as severe when presenting with an altered level of consciousness (Glasgow Coma Scale (GCS) < 15) or visual involvement. RESULTS: A total of 71 PA cases were identified, of whom 80.28% (n = 57) were classified as severe PA. The median age was 60 (18 to 85 years old) and 67.6% (n = 48) were male. Most patients had macroadenomas, except for one patient with a microadenoma of 9 mm. Headache was the most common presenting symptom (90.1%) and anticoagulation was the most frequent predisposing risk factor, but it was not associated with a higher risk for severe PA (odds ratio [OR] 1.13 [0.21-5.90]). Severe cases were associated with male gender (OR 5.53 [1.59-19.27]), tumor size >20 mm (OR 17.67 [4.07-76.64]), and Knosp grade ≥2 (OR 9.6 [2.38-38.73]). In the multivariant analysis, the only variables associated with a higher risk for severe PA were tumor size and Knosp grade. Surgery was more common in severe PA than in non-severe (91.2% vs. 64.3%, P = 0.009). CONCLUSION: A tumor size >20 mm and cavernous sinus invasion are risk factors for developing a severe PA. These risk factors can stratify patients at a higher risk of a worse clinical picture, and subsequently, more need of decompressive surgery.

Epigenetic differences between wild and cultivated grapevines highlight the contribution of DNA methylation during crop domestication.

The domestication process in grapevines has facilitated the fixation of desired traits. Nowadays, vegetative propagation through cuttings enables easier preservation of these genotypes compared to sexual reproduction. Nonetheless, even with vegetative propagation, various phenotypes are often present within the same vineyard due to the accumulation of somatic mutations. These mutations are not the sole factors influencing phenotype. Alongside somatic variations, epigenetic variation has been proposed as a pivotal player in regulating phenotypic variability acquired during domestication. The emergence of these epialleles might have significantly influenced grapevine domestication over time. This study aims to investigate the impact of domestication on methylation patterns in cultivated grapevines. Reduced-representation bisulfite sequencing was conducted on 18 cultivated and wild accessions. Results revealed that cultivated grapevines exhibited higher methylation levels than their wild counterparts. Differential Methylation Analysis between wild and cultivated grapevines identified a total of 9955 differentially methylated cytosines, of which 78% were hypermethylated in cultivated grapevines. Functional analysis shows that core methylated genes (consistently methylated in both wild and cultivated accessions) are associated with stress response and terpenoid/isoprenoid metabolic processes. Meanwhile, genes with differential methylation are linked to protein targeting to the peroxisome, ethylene regulation, histone modifications, and defense response. Collectively, our results highlight the significant roles that epialleles may have played throughout the domestication history of grapevines.

SEOM-GEMCAD-TTD clinical guidelines for the management of hepatocarcinoma patients (2023).

Hepatocellular carcinoma (HCC) is the most common primary malignancy in the liver and is the third cause of cancer-related death worldwide. Surveillance with abdominal ultrasound should be offered to individuals at high risk for developing HCC. Accurate diagnosis, staging, and liver function are crucial when determining the optimal therapeutic approach. The BCLC staging system is widely endorsed in Western countries. Managing this pathology requires a multidisciplinary, personalized approach, generally with a multimodal strategy. Surgery remains the only curative option, albeit local and systemic therapy may also increase survival when surgery is not suitable. In advanced disease, systemic treatment should be offered to patients with ECOG/PS 0-1 and Child-Pugh class A.

Source apportionment of ambient pollution levels in Guayaquil, Ecuador.

In this study, the relative contributions of main emission sources to the typical ambient concentrations of key pollutants, such as sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and particulate matter (PM10 and PM2.5) in Guayaquil, Ecuador, were investigated. A previous urban emissions inventory for mobile sources was expanded to include other transportation means and main industrial activities using the EMEP/EEA methodology to achieve this objective. The WRF/CALMET/CALPUFF modeling system was used to simulate the annual spatiotemporal distribution of air pollution in the city. According to the model, NO2 concentrations exceed the yearly value and 1-h Ecuadorian standards (40 and 200 µg/m3) in 1 % and 6 % of the cells of the modeling domain, respectively. These hotspots related to local sources were located in the northwest center of the city. The contributions of the manufacturing sector, thermal power plants, ports, airports, and road traffic were assessed individually, and the results indicated that air quality in the study area was strongly dominated by road traffic. The contributions of NO2, CO, PM10, and PM2.5 at the city level reached 76 %, 96 %, 90 %, and 92 % of the annual mean, respectively. In the case of SO2, the manufacturing sector made the most significant contribution (75 %), followed by thermal power plants (16 %). Furthermore, an analysis at 14 specific locations across Guayaquil identified spatial variations that may support the design and development of an air quality monitoring network for the city.

Signal execution modes emerge in biochemical reaction networks calibrated to experimental data.

Mathematical models of biomolecular networks are commonly used to study cellular processes; however, their usefulness to explain and predict dynamic behaviors is often questioned due to the unclear relationship between parameter uncertainty and network dynamics. In this work, we introduce PyDyNo (Python dynamic analysis of biochemical networks), a non-equilibrium reaction-flux based analysis to identify dominant reaction paths within a biochemical reaction network calibrated to experimental data. We first show, in a simplified apoptosis execution model, that despite the thousands of parameter vectors with equally good fits to experimental data, our framework identifies the dynamic differences between these parameter sets and outputs three dominant execution modes, which exhibit varying sensitivity to perturbations. We then apply our methodology to JAK2/STAT5 network in colony-forming unit-erythroid (CFU-E) cells and provide previously unrecognized mechanistic explanation for the survival responses of CFU-E cell population that would have been impossible to deduce with traditional protein-concentration based analyses.