Interesting Cytokine Profile Caused by Clinical Strains of Pseudomonas aeruginosa MDR Carrying the exoU Gene.

Pseudomonas aeruginosa is an opportunistic pathogen in HAIs with two facets: the most studied is the high rate of antimicrobial resistance, and the less explored is the long list of virulence factors it possesses. This study aimed to characterize the virulence genes carried by strains as well as the profile of cytokines related to inflammation, according to the resistance profile presented. This study aims to identify the virulence factors associated with MDR strains, particularly those resistant to carbapenems, and assess whether there is a cytokine profile that correlates with these characteristics. As methodology species were identified by classical microbiological techniques and confirmed by molecular biology, resistance levels were determined by the minimum inhibitory concentration and identification of MDR strains. Virulence factor genotyping was performed using PCR. In addition, biofilm production was assessed using crystal violet staining. Finally, the strains were cocultured with PBMC, and cell survival and the cytokines IL-1ß, IL-6, IL-10, IL-8, and TNF-α were quantified using flow cytometry. Bacteremia and nosocomial pneumonia in adults are the most frequent types of infection. In the toxigenic aspect, genes corresponding to the type III secretion system were present in at least 50% of cases. In addition, PBMC exposed to strains of four different categories according to their resistance and toxicity showed a differential pattern of cytokine expression, a decrease in IL-10, IL-6, and IL-8, and an over-secretion of IL-1b. In conclusion, the virulence genes showed a differentiated appearance for the two most aggressive exotoxins of T3SS (exoU and exoS) in multidrug-resistant strains. Moreover, the cytokine profile displays a low expression of cytokines with anti-inflammatory and proinflammatory effects in strains carrying the exoU gene.

Machine Learning Prediction of Treatment Response to Biological Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis.

Background: Disease-modifying antirheumatic drugs (bDMARDs) have shown efficacy in treating Rheumatoid Arthritis (RA). Predicting treatment outcomes for RA is crucial as approximately 30% of patients do not respond to bDMARDs and only half achieve a sustained response. This study aims to leverage machine learning to predict both initial response at 6 months and sustained response at 12 months using baseline clinical data. Methods: Baseline clinical data were collected from 154 RA patients treated at the University Hospital in Erlangen, Germany. Five machine learning models were compared: Extreme Gradient Boosting (XGBoost), Adaptive Boosting (AdaBoost), K-nearest neighbors (KNN), Support Vector Machines (SVM), and Random Forest. Nested cross-validation was employed to ensure robustness and avoid overfitting, integrating hyperparameter tuning within its process. Results: XGBoost achieved the highest accuracy for predicting initial response (AUC-ROC of 0.91), while AdaBoost was the most effective for sustained response (AUC-ROC of 0.84). Key predictors included the Disease Activity Score-28 using erythrocyte sedimentation rate (DAS28-ESR), with higher scores at baseline associated with lower response chances at 6 and 12 months. Shapley additive explanations (SHAP) identified the most important baseline features and visualized their directional effects on treatment response and sustained response. Conclusions: These findings can enhance RA treatment plans and support clinical decision-making, ultimately improving patient outcomes by predicting response before starting medication.

Sweet Cherry Plants Prioritize Their Response to Cope with Summer Drought, Overshadowing the Defense Response to Pseudomonas syringae pv. syringae.

Disease severity and drought due to climate change present significant challenges to orchard productivity. This study examines the effects of spring inoculation with Pseudomonas syringae pv. syringae (Pss) on sweet cherry plants, cvs. Bing and Santina with varying defense responses, assessing plant growth, physiological variables (water potential, gas exchange, and plant hydraulic conductance), and the levels of abscisic acid (ABA) and salicylic acid (SA) under two summer irrigation levels. Pss inoculation elicited a more pronounced response in 'Santina' compared to 'Bing' at 14 days post-inoculation (dpi), and those plants inoculated with Pss exhibited a slower leaf growth and reduced transpiration compared to control plants during 60 dpi. During differential irrigations, leaf area was reduced 14% and 44% in Pss inoculated plants of 'Bing' and 'Santina' respectively, under well-watered (WW) conditions, without changes in plant water status or gas exchange. Conversely, water-deficit (WD) conditions led to gas exchange limitations and a 43% decrease in plant biomass compared to that under WW conditions, with no differences between inoculation treatments. ABA levels were lower under WW than under WD at 90 dpi, while SA levels were significantly higher in Pss-inoculated plants under WW conditions. These findings underscore the influence on plant growth during summer in sweet cherry cultivars that showed a differential response to Pss inoculations and how the relationship between ABA and SA changes in plant drought level responses.

Partial sensory rhizotomy in recurrent trigeminal neuralgia. Our experience and literature review.

BACKGROUND AND OBJECTIVE: Trigeminal Neuralgia (NT) is a common pathology in Neurosurgery. It can be classified as idiopathic or secondary to other pathologies, such as Multiple Sclerosis (MS). Several surgical treatments have been described, some of them being replaced by more modern techniques. Partial sensory rhizotomy (PSR), described by Dandy is a technique replaced by other techniques due to its permanent side effects. We present our experience with this technique in patients with recurrent NT. METHODS AND MATERIALS: A retrospective review is carried out on five patients who underwent surgery at our center from 2018 to 2023 using the PSR technique. RESULTS: All the patients intervened showed significant clinical improvement, except one patient who required reintervention due to uncontrolled pain. According to the Barrow Neurological Institute (BNI) scale, 80% (4/5) of patients showed improvement from grade V to grades I/II except for one of them. This patient suffered from MS. Additionally, one patient presented a corneal ulcer after surgery due to impairment of the corneal reflex. CONCLUSION: In our experience, PSR is a valid treatment option in selected patients with recurrent TN. It has a low incidence of complications with an adequate surgical technique and anatomical knowledge of the region. To the best of our knowledge, we are one of the few centers in Spain to publish our results with PSR in the last ten years. We report good results in pain control withdrawing medication in 80% (4/5) of the operated patients.

Mobile App for Enhanced Anterior Cruciate Ligament (ACL) Assessment in Conscious Subjects: "Pivot-Shift Meter".

Anterior cruciate ligament (ACL) instability poses a considerable challenge in traumatology and orthopedic medicine, demanding precise diagnostics for optimal treatment. The pivot-shift test, a pivotal assessment tool, relies on subjective interpretation, emphasizing the need for supplementary imaging. This study addresses this limitation by introducing a machine learning classification algorithm integrated into a mobile application, leveraging smartphones' built-in inertial sensors for dynamic rotational stability assessment during knee examinations. Orthopedic specialists conducted knee evaluations on a cohort of 52 subjects, yielding valuable insights. Quantitative analyses, employing the Intraclass Correlation Coefficient (ICC), demonstrated robust agreement in both intraobserver and interobserver assessments. Specifically, ICC values of 0.94 reflected strong concordance in the timing between maneuvers, while signal amplitude exhibited consistency, with the ICC ranging from 0.71 to 0.66. The introduced machine learning algorithms proved effective, accurately classifying 90% of cases exhibiting joint hypermobility. These quantifiable results underscore the algorithm's reliability in assessing knee stability. This study emphasizes the practicality and effectiveness of implementing machine learning algorithms within a mobile application, showcasing its potential as a valuable tool for categorizing signals captured by smartphone inertial sensors during the pivot-shift test.

Can upwelling regions be potential thermal refugia for marine fishes during climate warming?

Species are expected to migrate to higher latitudes as warming intensifies due to anthropogenic climate change since physiological mechanisms have been adapted to maximize fitness under specific temperatures. However, literature suggests that upwellings could act as thermal refugia under climate warming protecting marine ecosystem diversity. This research aimed to predict the effects of climate warming on commercial and non-commercial fish species reported in official Mexican documents (>200 species) based on their thermal niche to observe if upwellings can act as potential thermal refugia. Present (2000-2014) and Representative Concentration Pathway (6.0 and 8.5) scenarios (2040-2050 and 2090-2100) have been considered for this work. Current and future suitability patterns, species distribution, richness, and turnover were calculated using the minimum volume ellipsoids as algorithm. The results in this study highlight that beyond migration to higher latitudes, upwelling regions could protect marine fishes, although the mechanism differed between the innate characteristics of upwellings. Most modeled species (primarily tropical fishes) found refuge in the tropical upwelling in Northern Yucatan. However, the highest warming scenario overwhelmed this region. In contrast, the Baja California region lies within the Eastern Boundary Upwelling Systems. While the area experiences an increase in suitability, the northern regions have a higher upwelling intensity acting as environmental barriers for many tropical species. Conversely, in the southern regions where upwelling is weaker, species tend to congregate and persist even during elevated warming, according to the turnover analysis. These findings suggest that tropicalization in higher latitudes may not be as straightforward as previously assumed. Nevertheless, climate change affects numerous ecosystem features, such as trophic relationships, phenology, and other environmental variables not considered here. In addition, uncertainty still exists about the assumption of increasing intensity of upwelling systems.

Heterogeneous gene expression during early arteriovenous fistula remodeling suggests that downregulation of metabolism predicts adaptive venous remodeling.

Clinical outcomes of arteriovenous fistulae (AVF) for hemodialysis remain inadequate since biological mechanisms of AVF maturation and failure are still poorly understood. Aortocaval fistula creation (AVF group) or a sham operation (sham group) was performed in C57BL/6 mice. Venous limbs were collected on postoperative day 7 and total RNA was extracted for high throughput RNA sequencing and bioinformatic analysis. Genes in metabolic pathways were significantly downregulated in the AVF, whereas significant sex differences were not detected. Since gene expression patterns among the AVF group were heterogenous, the AVF group was divided into a 'normal' AVF (nAVF) group and an 'outliers' (OUT) group. The gene expression patterns of the nAVF and OUT groups were consistent with previously published data showing venous adaptive remodeling, whereas enrichment analyses showed significant upregulation of metabolism, inflammation and coagulation in the OUT group compared to the nAVF group, suggesting the heterogeneity during venous remodeling reflects early gene expression changes that may correlate with AVF maturation or failure. Early detection of these processes may be a translational strategy to predict fistula failure and reduce patient morbidity.

Could titanium screws be an appropriate disc stabilization technique in temporomandibular joint arthroscopy?

Multiple techniques for disc fixation through temporomandibular joint arthroscopy have been described. They can be classified as non-rigid, semi-rigid, and rigid. They all offer different advantages and disadvantages, and some have greater difficulties than others. Currently, multiple modifications to the basic techniques have been described in order to facilitate the technique since disc fixation corresponds to one of the procedures that most require skill. However, each technique requires extensive evaluation and monitoring in order to avoid complications and find the benefits of each technique. For this reason, the objective of this letter to the editor is to discuss two situations observed in the previously described fixation technique with osteosynthesis screws. The first issue is the fixation mechanism, and the second is the fixation time. This is in order to continue searching for the truth among all to achieve the best results and the benefit of patients.

Targeted next-generation sequencing panel to investigate antiplatelet adverse reactions in acute coronary syndrome patients undergoing percutaneous coronary intervention with stenting.

Antiplatelet therapy, the gold standard of care for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), is one of the therapeutic approaches most associated with the development of adverse drug reactions (ADRs). Although numerous studies have shown that pharmacological intervention based on a limited number of high-evidence variants (primarily CYP2C19*2 and *3) can reduce the incidence of major adverse cardiovascular events (MACEs), ADRs still occur at variable rates (10.1 % in our case) despite personalized therapy. This study aimed to identify novel genetic variants associated with the endpoint of MACEs 12 months after PCI by designing and analyzing a targeted gene panel. We sequenced 244 ACS-PCI-stent patients (109 with event and 135 without event) and 99 controls without structural cardiovascular disease and performed an association analysis to search for unexpected genetic variants. No single nucleotide polymorphisms reached genomic significance after correction, but three novel variants, including ABCA1 (rs2472434), KLB (rs17618244), and ZNF335 (rs3827066), may play a role in MACEs in ACS patients. These genetic variants are involved in regulating high-density lipoprotein levels and cholesterol deposition, and as they are regulatory variants, they may affect the expression of nearby lipid metabolism-related genes. Our findings suggest new targets (both at the gene and pathway levels) that may increase susceptibility to MACEs, but further research is needed to clarify the role and impact of the identified variants before these findings can be incorporated into the therapeutic decision-making process.

Drug repositioning identifies histone deacetylase inhibitors that promote innate immunity in non-tuberculous mycobacterial infection.

Non-tuberculosis infections in immunocompromised patients represent a cause for concern, given the increased risks of infection, and limited treatments available. Herein, we report that molecules for binding to the catalytic site of histone deacetylase (HDAC) inhibit its activity, thus increasing the innate immune response against environmental mycobacteria. The action of HDAC inhibitors (iHDACs) was explored in a model of type II pneumocytes and macrophages infection by Mycobacterium aurum. The results show that the use of 1,3-diphenylurea increases the expression of the TLR-4 in M. aurum infected MDMs, as well as the production of defb4, IL-1ß, IL-12, and IL-6. Moreover, we observed that aminoacetanilide upregulates the expression of TLR-4 together with TLR-9, defb4, CAMP, RNase 6, RNase 7, IL-1ß, IL-12, and IL-6 in T2P. Results conclude that the tested iHDACs selectively modulate the expression of cytokines and antimicrobial peptides that are associated with reduction of non-tuberculous mycobacteria infection.

Acute Kidney Injury in the Context of COVID-19: An Analysis in Hospitalized Mexican Patients.

During the COVID-19 pandemic, a considerable proportion of patients developed a severe condition that included respiratory failure, shock, or multiple organ dysfunction. Acute Kidney Injury (AKI) has been recognized as a possible cause of severe COVID-19 development. Given this, this study investigates the occurrence and consequences of AKI in Mexican patients to contribute to better knowledge and management of this problem. Methods: Using a retrospective observational cohort methodology, we investigated 313 cases from a cohort of 1019 patients diagnosed with COVID-19 at the IMSS Zacatecas General Hospital of Zone No. 1 in 2020. The prevalence of AKI was determined using the AKIN criteria based on serum creatinine levels and a detailed review of demographic characteristics, medical history, comorbidities, and clinical development. Results: The data showed a 25.30% prevalence of AKI among patients infected with severe COVID-19. Remarkably, these patients with AKI exhibited an advanced age (>65 years), arterial hypertension, a higher number of white blood cells during admission and the hospital stay, and elevated levels of C-reactive protein, serum creatinine, and blood urea nitrogen (BUN). Clinically, patients with AKI had signs of prostration, pneumonia, and the requirement for ventilatory assistance when compared to those without AKI. Finally, those diagnosed with AKI and COVID-19 had a 74% death rate. Relative risk analyses indicated that age (>65 years), arterial hypertension, high creatinine levels, endotracheal intubation, and pneumonia are associated with the development of AKI. On the other hand, among the protective factors against AKI, high hemoglobin levels and the consumption of statins during COVID-19 were found. Conclusions: The findings of this study underscore the significance of promptly identifying and effectively managing AKI to potentially alleviate the negative consequences of this complication within the Mexican population during COVID-19.

Mutational landscape of risk variants in comorbid depression and obesity: a next-generation sequencing approach.

Major depression (MD) and obesity are complex genetic disorders that are frequently comorbid. However, the study of both diseases concurrently remains poorly addressed and therefore the underlying genetic mechanisms involved in this comorbidity remain largely unknown. Here we examine the contribution of common and rare variants to this comorbidity through a next-generation sequencing (NGS) approach. Specific genomic regions of interest in MD and obesity were sequenced in a group of 654 individuals from the PISMA-ep epidemiological study. We obtained variants across the entire frequency spectrum and assessed their association with comorbid MD and obesity, both at variant and gene levels. We identified 55 independent common variants and a burden of rare variants in 4 genes (PARK2, FGF21, HIST1H3D and RSRC1) associated with the comorbid phenotype. Follow-up analyses revealed significantly enriched gene-sets associated with biological processes and pathways involved in metabolic dysregulation, hormone signaling and cell cycle regulation. Our results suggest that, while risk variants specific to the comorbid phenotype have been identified, the genes functionally impacted by the risk variants share cell biological processes and signaling pathways with MD and obesity phenotypes separately. To the best of our knowledge, this is the first study involving a targeted sequencing approach toward the study of the comorbid MD and obesity. The framework presented here allowed a deep characterization of the genetics of the co-occurring MD and obesity, revealing insights into the mutational and functional profile that underlies this comorbidity and contributing to a better understanding of the relationship between these two disabling disorders.

Pseudomonas aeruginosa Isolates from Water Samples of the Gulf of Mexico Show Similar Virulence Properties but Different Antibiotic Susceptibility Profiles than Clinical Isolates.

Pseudomonas aeruginosa is an opportunistic pathogen found in a wide variety of environments, including soil, water, and habitats associated with animals, humans, and plants. From a One Health perspective, which recognizes the interconnectedness of human, animal, and environmental health, it is important to study the virulence characteristics and antibiotic susceptibility of environmental bacteria. In this study, we compared the virulence properties and the antibiotic resistance profiles of seven isolates collected from the Gulf of Mexico with those of seven clinical strains of P. aeruginosa. Our results indicate that the marine and clinical isolates tested exhibit similar virulence properties; they expressed different virulence factors and were able to kill Galleria mellonella larvae, an animal model commonly used to analyze the pathogenicity of many bacteria, including P. aeruginosa. In contrast, the clinical strains showed higher antibiotic resistance than the marine isolates. Consistently, the clinical strains exhibited a higher prevalence of class 1 integron, an indicator of anthropogenic impact, compared with the marine isolates. Thus, our results indicate that the P. aeruginosa marine strains analyzed in this study, isolated from the Gulf of Mexico, have similar virulence properties, but lower antibiotic resistance, than those from hospitals.

Differences between parents' and paediatricians' perceptions of mild respiratory infections in childhood: contrast study.

Introduction: Mild respiratory infections are a common reason for consultation in paediatrics, both in the emergency department and in primary care clinics. These conditions, mostly viral and self-limiting, have a significant impact on the healthcare system, school and work absenteeism, and family routines. Despite being common and banal illnesses from a medical perspective, they involve a significant concern in families. The main objective of the contrast study was to compare the perceptions of parents and paediatricians regarding mild respiratory infections in childhood and their impact on family conciliation. Materials and methods: Two online, cross-sectional surveys were conducted among Spanish paediatricians and parents with children aged 6 months to 12 years, involving 504 paediatricians and 1,447 families, with questions on attitudes towards visits to the paediatric consultation, care burden of minor pathologies, work, and family conciliation, and treatment and prevention of these illnesses. Results: Results showed significant differences in paediatricians' and parents' perceptions in many aspects. According to 34.5% of paediatricians and 27% of parents, families regularly go to the paediatrician without a scheduled visit. Only 4% of parents report having self-medicated their child, while paediatricians raise this percentage significantly to 48%. Regarding the question: "it is normal for a child to have an average of 4 colds a year," only 25.5% of the surveyed families "strongly agree" unlike to 70.2% of paediatricians. 72.8% of paediatricians "strongly agree" with: "in my opinion, it is good for children to get sick to improve their immune system" reduced to 45.9% of parents. Consultations for minor pathologies represent a "high workload" for 60.9% of paediatricians, while this opinion is agreed by only 18.9% of the parents. Conclusion: Mild respiratory infections in childhood are perceived differently by paediatricians and parents. While paediatricians perceive them as a common and manageable phenomenon, parents tend to show higher concern and demand for medical attention. This study underlines the need to improve communication between paediatricians and parents to align perceptions, optimise the use of the health system resources, and improve the efficiency in the management of these common paediatric illnesses.

An atlas of spider development at single-cell resolution provides new insights into arthropod embryogenesis.

Spiders are a diverse order of chelicerates that diverged from other arthropods over 500 million years ago. Research on spider embryogenesis, particularly studies using the common house spider Parasteatoda tepidariorum, has made important contributions to understanding the evolution of animal development, including axis formation, segmentation, and patterning. However, we lack knowledge about the cells that build spider embryos, their gene expression profiles and fate. Single-cell transcriptomic analyses have been revolutionary in describing these complex landscapes of cellular genetics in a range of animals. Therefore, we carried out single-cell RNA sequencing of P. tepidariorum embryos at stages 7, 8 and 9, which encompass the establishment and patterning of the body plan, and initial differentiation of many tissues and organs. We identified 20 cell clusters, from 18.5 k cells, which were marked by many developmental toolkit genes, as well as a plethora of genes not previously investigated. We found differences in the cell cycle transcriptional signatures, suggestive of different proliferation dynamics, which related to distinctions between endodermal and some mesodermal clusters, compared with ectodermal clusters. We identified many Hox genes as markers of cell clusters, and Hox gene ohnologs were often present in different clusters. This provided additional evidence of sub- and/or neo-functionalisation of these important developmental genes after the whole genome duplication in an arachnopulmonate ancestor (spiders, scorpions, and related orders). We also examined the spatial expression of marker genes for each cluster to generate a comprehensive cell atlas of these embryonic stages. This revealed new insights into the cellular basis and genetic regulation of head patterning, hematopoiesis, limb development, gut development, and posterior segmentation. This atlas will serve as a platform for future analysis of spider cell specification and fate, and studying the evolution of these processes among animals at cellular resolution.