Unveiling the microevolution of antimicrobial resistance in selected Pseudomonas aeruginosa isolates from Egyptian healthcare settings: A genomic approach.

The incidence of Pseudomonas aeruginosa infections in healthcare environments, particularly in low-and middle-income countries, is on the rise. The purpose of this study was to provide comprehensive genomic insights into thirteen P. aeruginosa isolates obtained from Egyptian healthcare settings. Phenotypic analysis of the antimicrobial resistance profile and biofilm formation were performed using minimum inhibitory concentration and microtiter plate assay, respectively. Whole genome sequencing was employed to identify sequence typing, resistome, virulome, and mobile genetic elements. Our findings indicate that 92.3% of the isolates were classified as extensively drug-resistant, with 53.85% of these demonstrating strong biofilm production capabilities. The predominant clone observed in the study was ST773, followed by ST235, both of which were associated with the O11 serotype. Core genome multi-locus sequence typing comparison of these clones with global isolates suggested their potential global expansion and adaptation. A significant portion of the isolates harbored Col plasmids and various MGEs, all of which were linked to antimicrobial resistance genes. Single nucleotide polymorphisms in different genes were associated with the development of antimicrobial resistance in these isolates. In conclusion, this pilot study underscores the prevalence of extensively drug-resistant P. aeruginosa isolates and emphasizes the role of horizontal gene transfer facilitated by a diverse array of mobile genetic elements within various clones. Furthermore, specific insertion sequences and mutations were found to be associated with antibiotic resistance.

Structural heart transcatheter interventions in orthotopic cardiac transplant and left ventricular assist devices recipients: A nationwide study.

BACKGROUND: The current incidence and outcomes of structural transcatheter procedures in heart transplant (HTx) recipients and left-ventricular assist devices (LVAD) carriers is unknown. AIMS: To provide insights on structural transcatheter procedures performed across HTx and LVAD patients in Spain. METHODS: Multicenter, ambispective, observational nationwide registry. RESULTS: Until May/2023, 36 percutaneous structural interventions were performed (78% for HTx and 22% for LVAD) widely varying among centers (0%-1.4% and 0%-25%, respectively). Percutaneous mitral transcatheter edge-to-edge (TEER) was the most common (n = 12, 33.3%), followed by trancatheter aortic valve replacement (n = 11, 30.5%), and tricuspid procedures (n = 9, 25%). Mitral TEER resulted in mild residual mitral regurgitation in all but one case, mean gradient was <5 mmHg in 75% of them at 1-year, with no mortality and 8.3% re-admission rate. Tricuspid TEER resulted in 100% none/mild residual regurgitation with a 1-year mortality and readmission rates of 22% and 28.5%, respectively. Finally, trancatheter aortic valve replacement procedures (n = 8 in LVADs due to aortic regurgitation and n = 3 in HTx), were successful in all cases with one prosthesis degeneration leading to severe aortic regurgitation at 1-year, 18.2% mortality rate and no re-admissions. Globally, major bleeding rates were 7.9% and 12.5%, thromboembolic events 3.7% and 12.5%, readmissions 37% and 25%, and mortality 22% and 25%, in HTx and LVADs respectively. No death was related to the implanted transcatheter device. CONCLUSIONS: Most centers with HTx/LVAD programs perform structural percutaneous procedures but with very inconsistent incidence. They were associated with good safety and efficacy, but larger studies are required to provide formal recommendations.

The resistome of the food chain: A One Health perspective.

Antimicrobial resistance (AMR) represents a significant global health problem which challenges Sustainable Development Goal 3 of the United Nations, with growing concerns about the possibility of AMR transmission through the food chain. The indiscriminate use of antimicrobials for the treatment of food production animals and for agricultural crop improvement, in addition to the direct discharge of livestock farm residues to sewage and the use of animal manure in agriculture, are among the factors that can facilitate the selection and transmission of AMR throughout the food chain. The study of food microbiomes has been boosted by the advent of next-generation sequencing techniques, which have enabled gaining in-depth understanding of the diversity of antimicrobial resistance genes present in food and associated environments (the so-called resistome). The aim of this review is to provide an accurate and comprehensive overview of the knowledge currently available on the resistome of the most frequently consumed foods worldwide, from a One Health perspective. To this end, the different metagenomic studies which have been conducted to characterize the resistome of foods are compiled and critically discussed.

Effects of Developmental Timing on Cognitive and Behavioral Profiles in Fetal Alcohol Spectrum Disorder: Considerations for Education.

Associations and families demand the need to raise awareness of the implications in the cognitive and behavioral development of children with Fetal Alcohol Spectrum Disorder (FASD) that affect their learning and school participation. This study aims to generate a profile of executive and behavioral functioning in children and adolescents diagnosed with FASD. A probabilistic sampling by clusters (associations for individuals with FASD) is applied. The sample is composed of 66 families from three associations. The BRIEF-2 and SENA tests were administered to assess executive and behavioral functioning domains. Data analysis found that the executive and behavioral functioning profile of individuals with FASD varies with age, with greater impairment in middle and late adolescence. Likewise, the domain of executive functioning most affected in any of the developmental stages is working memory. Finally, cognitive impairment in the executive functioning domains has a direct impact on the social and adaptive functioning of people with FASD.

Do High Doses of Multiple Antibiotics Loaded into Bone Cement Spacers Improve the Success Rate in Staphylococcal Periprosthetic Joint Infection When Rifampicin Cannot Be Employed?

Rifampicin is one of the mainstays in treating staphylococcal prosthetic joint infection (PJI). However, discontinuation due to intolerance, drug interactions, and adverse events is common. Two-stage revision surgery remains the gold standard, with the number of revision arthroplasties steadily increasing. This study aims to evaluate the effectiveness and safety of a novel two-stage revision protocol for staphylococcal prosthetic joint infection (PJI) utilizing bone cement spacers loaded with multiple high doses of antibiotics. Additionally, it seeks to analyze outcomes in patients ineligible for rifampicin treatment. A retrospective review of 43 cases of staphylococcal hip and knee prosthetic joint infections (PJIs) from 2012 to 2020 was conducted. In all instances, a commercial cement containing 1 g of gentamicin and 1 g of clindamycin, augmented with 4 g of vancomycin and 2 g of ceftazidime, was employed to cast a spacer manually after thorough surgical debridement. We report an eradication rate of 82%, with no significant differences observed (p = 0.673) between patients treated with (84%, n = 19) and without rifampicin (79%, n = 24). There were no disparities in positive culture rates (7%), spacer replacement (18%), or survival analysis (p = 0.514) after an average follow-up of 68 months (range 10-147) in the absence of systemic toxicity and surgical complications superimposable to those previously reported. In conclusion, two-stage revision with local high doses of ceftazidime, vancomycin, gentamicin, and clindamycin demonstrates high effectiveness in treating staphylococcal PJIs. Notably, systemic rifampicin does not influence the outcomes. This protocol, with multiple high doses of antibiotics loaded into the bone cement spacer, is presented as a viable and safe alternative for patients unsuitable for rifampicin treatment.

HIV status and substance use disorder treatment need and utilization among adults in the United States, 2015-2019: Implications for healthcare service provision and integration.

INTRODUCTION: Substance use disorders (SUD) are associated with HIV acquisition and care disruptions. Most research focuses on clinical samples; however, we used a nationally representative, community-based sample to estimate SUD treatment need and utilization by HIV status. METHODS: We included participants from the 2015-2019 National Survey on Drug Use and Health aged 18 and older who met past-year DSM-IV SUD criteria (n = 22,166). Participants self-reported whether a healthcare professional ever told them they had HIV or AIDS [i.e., people with HIV (PWH), non-PWH, HIV status unknown]. Outcomes included past-year: 1) any SUD treatment use; 2) any specialty SUD treatment use; and 3) perceived SUD treatment need. Survey weighted multivariable logistic regression models estimated the likelihood of each outcome by HIV status, adjusting for age, sex, race/ethnicity, education, survey year, health insurance status, and household income. RESULTS: Overall, 0.5 % were PWH and 0.8 % had an HIV unknown status. Any past-year SUD treatment utilization was low across all groups (10.3 % non-PWH, 24.2 % PWH, and 17.3 % HIV status unknown respondents). Specialty SUD treatment utilization was reported by 7.2 % of non-PWH, 17.8 % PWH, and 10.9 % HIV status unknown respondents. Perceived treatment need was reported by 4.9 % of non-PWH, 12.4 % of PWH, and 3.7 % of HIV status unknown respondents. In adjusted models, PWH were more likely than non-PWH to report any past-year SUD treatment utilization (aOR = 2.06; 95 % CI = 1.08-3.94) or past-year specialty SUD treatment utilization (aOR = 2.07; 95 % CI = 1.07-4.01). Among those with a drug use disorder other than cannabis, respondents with HIV-unknown status were less likely than HIV-negative individuals to report past-year perceived treatment need (aOR = 0.39; 95 % CI = 0.20-0.77). CONCLUSIONS: Despite high SUD treatment need among PWH, more than three quarters of PWH with SUD reported no past-year treatment. Compared to non-PWH, PWH had higher treatment utilization and higher specialty treatment utilization, but SUD treatment was low across all groups. As SUD is associated with adverse HIV outcomes, our findings highlight the need for the integration of SUD treatment with HIV testing and care. Increasing access to SUD treatment could help reduce negative SUD-related outcomes along the HIV care continuum.

Disease-associated comorbidities, medication records and anthropometric measures in adults with Duchenne muscular dystrophy.

We investigated the comorbidities, associated factors, and the relationship between anthropometric measures and respiratory function and functional abilities in adults with Duchenne muscular dystrophy (DMD). This was a single-centre cross-sectional study in genetically diagnosed adults with DMD (>16 years old). Univariate and multivariate analyses identified factors associated with dysphagia, constipation, Body Mass Index (BMI), and weight. Regression analysis explored associations between BMI, weight, and respiratory/motor abilities. We included 112 individuals (23.4 ± 5.2 years old), glucocorticoid-treated 66.1 %. The comorbidities frequency was 61.6 % scoliosis (61.0 % of them had spinal surgery), 36.6 % dysphagia, 36.6 % constipation, and 27.8 % urinary conditions. The use of glucocorticoids delayed the time to spinal surgery. The univariate analysis revealed associations between dysphagia and constipation with age, lack of glucocorticoid treatment, and lower respiratory and motor function. In the multivariate analysis, impaired cough ability remained as the factor consistently linked to both conditions. Constipation associated with lower BMI and weight. BMI and weight positively correlated with respiratory parameters, but they did not associate with functional abilities. Glucocorticoids reduce the frequency of comorbidities in adults with DMD. The ability to cough can help identifying dysphagia and constipation. Lower BMI and weight in individuals with DMD with compromised respiratory function may suggest a higher calories requirement.

Venous valve hypoxia as a possible mechanism of deep vein thrombosis: a scoping review.

INTRODUCTION: The pathogenesis of deep vein thrombosis (DVT) has been explained by an interplay between a changed blood composition, vein wall alteration, and blood flow abnormalities. A comprehensive investigation of these components of DVT pathogenesis has substantially promoted our understanding of thrombogenesis in the venous system. Meanwhile, the process of DVT initiation remains obscure. This systematic review aims to collect, analyze, and synthesize the published evidence to propose hypoxia as a possible trigger of DVT. EVIDENCE ACQUISITION: An exhaustive literature search was conducted across multiple electronic databased including PubMed, EMBASE, Scopus, and Web of Science to identify studies pertinent to the research hypothesis. The search was aimed at exploring the connection between hypoxia, reoxygenation, and the initiation of deep vein thrombosis (DVT). The following key words were used: "deep vein thrombosis," "venous thrombosis," "venous thromboembolism," "hypoxia," "reoxygenation," "venous valve," and "venous endothelium." Reviews, case reports, editorials, and letters were excluded. EVIDENCE SYNTHESIS: Based on the systematic search outcome, 156 original papers relevant to the issue were selected for detailed review. These studies encompassed a range of experimental and observational clinical research, focusing on various aspects of DVT, including the anatomical, physiological, and cellular bases of the disease. A number of studies suggested limitations in the traditional understanding of Virchow's triad as an acceptable explanation for DVT initiation. Emerging evidence points to more complex interactions and additional factors that may be critical in the early stages of thrombogenesis. The role of venous valves has been recognized but remains underappreciated, with several studies indicating that these sites may act as primary loci for thrombus formation. A collection of studies describes the effects of hypoxia on venous endothelial cells at the cellular and molecular levels. Hypoxia influences several pathways that regulate endothelial cell permeability, inflammatory response, and procoagulation activity, underpinning the endothelial dysfunction noted in DVT. CONCLUSIONS: Hypoxia of the venous valve may serve as an independent hypothesis to outline the DVT triggering process. Further research projects in this field may discover new molecular pathways responsible for the disease and suggest new therapeutic targets.

Genome evolution and transcriptome plasticity is associated with adaptation to monocot and dicot plants in Colletotrichum fungi.

BACKGROUND: Colletotrichum fungi infect a wide diversity of monocot and dicot hosts, causing diseases on almost all economically important plants worldwide. Colletotrichum is also a suitable model for studying gene family evolution on a fine scale to uncover events in the genome associated with biological changes. RESULTS: Here we present the genome sequences of 30 Colletotrichum species covering the diversity within the genus. Evolutionary analyses revealed that the Colletotrichum ancestor diverged in the late Cretaceous in parallel with the diversification of flowering plants. We provide evidence of independent host jumps from dicots to monocots during the evolution of Colletotrichum, coinciding with a progressive shrinking of the plant cell wall degradative arsenal and expansions in lineage-specific gene families. Comparative transcriptomics of 4 species adapted to different hosts revealed similarity in gene content but high diversity in the modulation of their transcription profiles on different plant substrates. Combining genomics and transcriptomics, we identified a set of core genes such as specific transcription factors, putatively involved in plant cell wall degradation. CONCLUSIONS: These results indicate that the ancestral Colletotrichum were associated with dicot plants and certain branches progressively adapted to different monocot hosts, reshaping the gene content and its regulation.

Hemorrhagic Cholecystitis in a Patient Under Anticoagulant and Antiplatelet Therapy: A Case Report.

Hemorrhagic cholecystitis is an uncommon presentation of acute cholecystitis. Due to its etiology and unspecific clinical data, it is an entity that represents a diagnostic challenge. We present a case of a 70-year-old male with diabetes type 2, hypertension, and chronic kidney disease with hemodialysis, who attended the emergency department with sudden-onset abdominal pain in the epigastrium. The patient presented no additional symptoms, a normal electrocardiogram, but due to the characteristics of the pain and elevated troponin I, emergency medicine specialists considered an acute coronary syndrome and initiated antiplatelet and anticoagulant therapy. Due to persistent abdominal pain, a decrease in hemoglobin, and the onset of arterial hypotension, a computed tomography (CT) scan was performed, which revealed perforation of the gallbladder, apparent hemorrhagic cholecystitis, and hemoperitoneum. The patient underwent emergent surgery, where CT findings were confirmed. In our case, the suspicion of hemorrhagic cholecystitis arose until the clinical case was advanced, after receiving anticoagulant and antiplatelet therapy, and it was confirmed during surgery and with histopathology. This concludes that hemorrhagic cholecystitis is a rare disease and difficult to diagnose. Therefore, studies should focus on clinical presentation and risk factors (e.g., trauma, malignancy, renal failure, cirrhosis, and anticoagulation therapy) to promote early diagnosis and avoid complications.

Personality Traits and eHealth Study Enrollment Among Racial and Sexual Minoritized Men Living with HIV.

Inequities in eHealth research enrollment persist among Black and Latinx sexual minoritized men (SMM) partly due to socio-ecological barriers. Less is known about how personality traits are associated with their study enrollment. We examined the role of personality traits among 1,285 U.S. Black and Latinx SMM living with HIV recruited from sexual networking websites/apps for an eHealth intervention. Lower neuroticism and higher openness were associated with greater odds of study enrollment among Latinx SMM. Given these exploratory findings, future research should examine this phenomenon, along with well-established socio-ecological factors such as medical mistrust to better understand eHealth study enrollment gaps among Black and Latinx SMM.

Jawbone quality classification in dental implant planning and placement studies. A scoping review.

Aim: Cone beam computed tomography has become an attractive method for implant planning. However, in most cases, not all the information is taken advantage of and often the radiographic evaluation of bone quality is based on subjective assessment by the individual clinician. Therefore, the aim of this study was to examine classifications of bone tissue characteristics and methods for assessing them in dental implant planning and placement studies. Materials and Methods: Three databases (Pubmed, Scopus, Web of Science) were searched using specific index terms: "Bone quality, bone quantity, bone density, cone-beam CT and cone-beam computed tomography". Three reviewers selected titles and analyzed abstracts according to inclusion and exclusion criteria. Some descriptions of bone tissue characteristics (bone quality, density, and quantity) used before or during dental implant placement were selected and categorized. Results: The search yielded 442 titles. A total of 32 articles were selected and read in full text. Seventeen articles were considered relevant. Different classification systems were found to evaluate bone tissue characteristics as well as different examination protocols. Thirteen publications included in this review reported on bone quality and quantity using the Lekholm and Zarb classification. However, only four studies implemented and/or proposed modifications of the Lekholm and Zarb system. Four other publications described bone quality according to different classification systems such as Misch, University of California Los Angeles (UCLA), or Trisi and Rao. The assessment methods were often briefly described (or not described at all in one publication). Of the articles analyzed, five presented observer performance, whereas three presented diagnostic accuracy of the assessment method. Conclusion: Currently, there are different classification systems applied to dental implant planning and placement, particularly regarding whether bone quality or quantity affects treatment outcomes. However, most authors have not validated the diagnostic accuracy and reproducibility of the classification used. Therefore, it is necessary to develop a classification system consistent with characteristics of bone tissue, taking into consideration an adequate description of bone tissue assessment methods, their diagnostic accuracy, and observer performance.

Fine grain emotion analysis in Spanish using linguistic features and transformers.

Mental health issues are a global concern, with a particular focus on the rise of depression. Depression affects millions of people worldwide and is a leading cause of suicide, particularly among young people. Recent surveys indicate an increase in cases of depression during the COVID-19 pandemic, which affected approximately 5.4% of the population in Spain in 2020. Social media platforms such as X (formerly Twitter) have become important hubs for health information as more people turn to these platforms to share their struggles and seek emotional support. Researchers have discovered a link between emotions and mental illnesses such as depression. This correlation provides a valuable opportunity for automated analysis of social media data to detect changes in mental health status that might otherwise go unnoticed, thus preventing more serious health consequences. Therefore, this research explores the field of emotion analysis in Spanish towards mental disorders. There are two contributions in this area. On the one hand, the compilation, translation, evaluation and correction of a novel dataset composed of a mixture of other existing datasets in the bibliography. This dataset compares a total of 16 emotions, with an emphasis on negative emotions. On the other hand, the in-depth evaluation of this novel dataset with several state-of-the-art transformers based on encoder-only and encoder-decoder architectures. The analysis compromises monolingual, multilingual and distilled models as well as feature integration techniques. The best results are obtained with the encoder-only MarIA model, with a macro-average F1 score of 60.4771%.

Microbiome mapping in beef processing reveals safety-relevant variations in microbial diversity and genomic features.

The microbiome of surfaces along the beef processing chain represents a critical nexus where microbial ecosystems play a pivotal role in meat quality and safety of end products. This study offers a comprehensive analysis of the microbiome along beef processing using whole metagenomics with a particular focus on antimicrobial resistance and virulence-associated genes distribution. Our findings highlighted that microbial communities change dynamically in the different steps along beef processing chain, influenced by the specific conditions of each micro-environment. Brochothrix thermosphacta, Carnobacterium maltaromaticum, Pseudomonas fragi, Psychrobacter cryohalolentis and Psychrobacter immobilis were identified as the key species that characterize beef processing environments. Carcass samples and slaughterhouse surfaces exhibited a high abundance of antibiotic resistance genes (ARGs), mainly belonging to aminoglycosides, ß-lactams, amphenicols, sulfonamides and tetracyclines antibiotic classes, also localized on mobile elements, suggesting the possibility to be transmitted to human pathogens. We also evaluated how the initial microbial contamination of raw beef changes in response to storage conditions, showing different species prevailing according to the type of packaging employed. We identified several genes leading to the production of spoilage-associated compounds, and highlighted the different genomic potential selected by the storage conditions. Our results suggested that surfaces in beef processing environments represent a hotspot for beef contamination and evidenced that mapping the resident microbiome in these environments may help in reducing meat microbial contamination, increasing shelf-life, and finally contributing to food waste restraint.

WLB-87848, a Selective σ1 Receptor Agonist, with an Unusually Positioned NH Group as Positive Ionizable Moiety and Showing Neuroprotective Activity.

The synthesis and pharmacological activity of a new series of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as sigma-1 receptor (σ1R) ligands are reported. A hit from a high-throughput screening program was evolved into a highly potent and selective σ1R agonist (14qR) that contains a free NH group as positive ionizable moiety, not fulfilling the usual pharmacophoric features of the σ1R. The compound shows good physicochemical and ADMET characteristics, displays an agonist profile in the binding immunoglobulin protein/σ1R association assay, induces neuron viability in an in vitro model of ß-amyloid peptide intoxication, and presents positive results against recognition memory impairment induced by hippocampal injection of Aß peptide in rats after oral treatment, altogether making 14qR (WLB-87848) an interesting candidate for neuroprotection.

Venous thromboembolism swine model with reflux-induced venous hypertension.

Objective: This study describes a novel swine model of venous thromboembolism (VTE) with reflux-induced venous hypertension. Methods: Six pigs underwent disruption of the tricuspid chordae tendineae to create reflux and venous hypertension in the femoral vein. The vein was traumatized 2 to 3 weeks later by repeated withdrawal of a slightly overinflated occlusion balloon across the lumen, followed by balloon occlusion of the outflow. A small amount of thrombin was injected into the traumatized vein segment immediately after outflow occlusion. Thrombosis of the traumatized vein evolved into an organized thrombus seven weeks later. The histological features of the harvested post-thrombotic femoral vein were studied with hematoxylin and eosin and Trichrome stains. Results: In all six pigs, initial disruption of the chordae tendineae was successfully performed to create tricuspid reflux and venous hypertension. After two-stage sequential procedures, a thrombus formed in the target femoral vein segment. Histology of the harvested thrombotic vein showed features of an organizing thrombus with collagen formation and fibrosis. Conclusions: The novel swine VTE model may serve as a platform for developing and testing human-sized therapeutic procedures and devices in translational venous research. Clinical Relevance: This study describes a swine model of VTE created by incorporating all three elements of Virchow's triad. The model uniquely incorporates reflux-induced venous hypertension, which may be used in studying venous insufficiency and VTE in those with systemic venous hypertension. Likewise, this model may serve as a platform for development and evaluation of diagnostic imaging or therapeutic procedures and devices in subjects with systemic venous hypertension.

Tradeoffs between bite force and gape in Eulemur and Varecia.

In 1974, Sue Herring described the relationship between two important performance variables in the feeding system, bite force and gape. These variables are inversely related, such that, without specific muscular adaptations, most animals cannot produce high bite forces at large gapes for a given sized muscle. Despite the importance of these variables for feeding biomechanics and functional ecology, the paucity of in vivo bite force data in primates has led to bite forces largely being estimated through ex vivo methods. Here, we quantify and compare in vivo bite forces and gapes with output from simulated musculoskeletal models in two craniofacially distinct strepsirrhines: Eulemur, which has a shorter jaw and slower chewing cycle durations relative to jaw length and body mass compared to Varecia. Bite forces were collected across a range of linear gapes from 16 adult lemurs (suborder Strepsirrhini) at the Duke Lemur Center in Durham, North Carolina representing three species: Eulemur flavifrons (n = 6; 3F, 3M), Varecia variegata (n = 5; 3F, 2M), and Varecia rubra (n = 5; 5F). Maximum linear and angular gapes were significantly higher for Varecia compared to Eulemur (p = .01) but there were no significant differences in recorded maximum in vivo bite forces (p = .88). Simulated muscle models using architectural data for these taxa suggest this approach is an accurate method of estimating bite force-gape tradeoffs in addition to variables such as fiber length, fiber operating range, and gapes associated with maximum force. Our in vivo and modeling data suggest Varecia has reduced bite force capacities in favor of absolutely wider gapes compared to Eulemur in relation to their longer jaws. Importantly, our comparisons validate the simulated muscle approach for estimating bite force as a function of gape in extant and fossil primates.