Micro-osteoperforation for enhancement of orthodontic movement: A mechanical analysis using the finite element method.

BACKGROUND: Micro-osteoperforation is a minimally invasive technique aimed at accelerating tooth movement. The goal of this novel experimental study was to assess tooth movement and stress distribution produced by the force of orthodontic movement on the tooth structure, periodontal ligament, and maxillary bone structure, with and without micro-osteoperforation, using the finite element method. MATERIALS AND METHODS: Cone-beam computed tomography was used to obtain a virtual model of the maxilla and simulate the extraction of right and left first premolars. Three micro-osteoperforations (1.5 x 5 mm) were made in the hemiarch on the distal and mesial surfaces of upper canines, according to the power tip geometry of the Propel device (Propel Orthodontics, Ossining, New York, USA). An isotropic model of the maxilla was fabricated according to the finite element method by insertion of mechanical properties of the tooth structures, with orthodontic force (1.5 N) simulation in the distal movement on the upper canine of a hemiarch. RESULTS: Initial movement was larger when micro-osteoperforations were performed on the dental crown (24%) and on the periodontal ligament (29%). In addition, stress distribution was higher on the bone structure (31%) when micro-osteoperforations were used. CONCLUSIONS: Micro-osteoperforations considerably increased the movement of both the dental crown and periodontal ligament, which highlights their importance in the improvement of orthodontic movement, as well as in stress distribution across the bone structure. Important stress absorption regions were identified within micro-osteoperforations.

Estimated number of lives directly saved by COVID-19 vaccination programmes in the WHO European Region from December, 2020, to March, 2023: a retrospective surveillance study.

BACKGROUND: By March, 2023, 54 countries, areas, and territories (hereafter CAT) in the WHO European Region had reported more than 2·2 million COVID-19-related deaths to the WHO Regional Office for Europe. Here, we estimated how many lives were directly saved by vaccinating adults in the WHO European Region from December, 2020, to March, 2023. METHODS: In this retrospective surveillance study, we estimated the number of lives directly saved by age group, vaccine dose, and circulating variant-of-concern (VOC) period, regionally and nationally, using weekly data on COVID-19 mortality and infection, COVID-19 vaccination uptake, and SARS-CoV-2 virus characterisations by lineage downloaded from The European Surveillance System on June 11, 2023, as well as vaccine effectiveness data from the literature. We included data for six age groups (25-49 years, 50-59 years, ≥60 years, 60-69 years, 70-79 years, and ≥80 years). To be included in the analysis, CAT needed to have reported both COVID-19 vaccination and mortality data for at least one of the four older age groups. Only CAT that reported weekly data for both COVID-19 vaccination and mortality by age group for 90% of study weeks or more in the full study period were included. We calculated the percentage reduction in the number of expected and reported deaths. FINDINGS: Between December, 2020, and March, 2023, in 34 of 54 CAT included in the analysis, COVID-19 vaccines reduced deaths by 59% overall (CAT range 17-82%), representing approximately 1·6 million lives saved (range 1·5-1·7 million) in those aged 25 years or older: 96% of lives saved were aged 60 years or older and 52% were aged 80 years or older; first boosters saved 51% of lives, and 60% were saved during the Omicron period. INTERPRETATION: Over nearly 2·5 years, most lives saved by COVID-19 vaccination were in older adults by first booster dose and during the Omicron period, reinforcing the importance of up-to-date vaccination among the most at-risk individuals. Further modelling work should evaluate indirect effects of vaccination and public health and social measures. FUNDING: US Centers for Disease Control and Prevention.

A Small TAT-TrkB Peptide Prevents BDNF Receptor Cleavage and Restores Synaptic Physiology in Alzheimer's Disease.

In Alzheimer's disease (AD), amyloid ß (Aß)-triggered cleavage of TrkB-FL impairs Brain-derived neurotrophic factor (BDNF) signaling, thereby compromising neuronal survival, differentiation, as well as synaptic transmission and plasticity. Using cerebrospinal fluid and post-mortem human brain samples, we show that TrkB-FL cleavage occurs from the early stages of the disease and increases as function of pathology severity. To explore the therapeutic potential of this disease mechanism, we designed small TAT-fused peptides and screened their ability to prevent TrkB-FL receptor cleavage. Among these, a TAT-TrkB peptide with a lysine-lysine linker prevented TrkB-FL cleavage both in vitro and in vivo and rescued synaptic deficits induced by oligomeric Aß in hippocampal slices. Furthermore, this TAT-TrkB peptide improved the cognitive performance, ameliorated synaptic plasticity deficits and prevented Tau pathology progression in vivo in the 5XFAD mouse model of AD. No evidence of liver or kidney toxicity was found. We provide proof-of-concept evidence for the efficacy and safety of this therapeutic strategy and anticipate that this TAT-TrkB peptide has the potential of a disease-modifying drug that can prevent and/or reverse cognitive deficits in patients with AD.

Recurrence of fusocellular subtype GIST with SDHB mutation: A case of SDHB-loss and therapeutic challenges.

Gastrointestinal stromal tumors (GISTs) are sarcomas affecting the stomach and small intestine, with a rare subtype characterized by succinate dehydrogenase B (SDHB)-loss posing significant diagnostic and therapeutic challenges. A 62-year-old man with weight loss and abdominal pain was diagnosed with a gastric GIST showing SDHB-loss. Initial treatment with Imatinib reduced the tumor size, but surgery revealed no residual tumor. Despite adjuvant Imatinib, recurrence occurred, necessitating further surgical intervention. While GISTs typically benefit from surgery and tyrosine kinase inhibitors (TKIs), those with SDHB-loss are resistant to TKIs, requiring a different management approach. This case emphasizes the importance of surgical intervention for SDHB-deficient GISTs and the need for ongoing research into effective treatments for this subtype.

Computer-aided drug design supporting sunscreen research: a showcase study using previously synthesized hybrid UV filter-antioxidant compounds.

CONTEXT: Although quantum mechanical calculations have proven effective in accurately predicting UV absorption and assessing the antioxidant potential of compounds, the utilization of computer-aided drug design (CADD) to support sustainable synthesis research of new sunscreen active ingredients remains an area with limited exploration. Furthermore, there are ongoing concerns about the safety and effectiveness of existing sunscreens. Therefore, it remains crucial to investigate photoprotection mechanisms and develop enhanced strategies for mitigating the harmful effects of UVR exposure, improving both the safety and efficacy of sunscreen products. A previous study conducted synthesis research on eight novel hybrid compounds (I-VIII) for use in sunscreen products by molecular hybridization of trans-resveratrol (RESV), avobenzone (AVO), and octinoxate (OMC). Herein, time-dependent density functional theory (TD-DFT) calculations performed in the gas phase on the isolated hybrid compounds (I-VIII) proved to reproduce the experimental UV absorption. Resveratrol-avobenzone structure-based hybrids (I-IV) present absorption maxima in the UVB range with slight differences between them, while resveratrol-OMC structure-based hybrids (V-VIII) showed main absorption in the UVA range. Among RESV-OMC hybrids, compounds V and VI exhibited higher UV absorption intensity, and compound VIII stood out for its broad-spectrum coverage in our simulations. Furthermore, both in silico and in vitro analyses revealed that compounds VII and VIII exhibited the highest antioxidant activity, with compound I emerging as the most reactive antioxidant within RESV-AVO hybrids. The study suggests a preference for the hydrogen atom transfer (HAT) mechanism over single-electron transfer followed by proton transfer (SET-PT) in the gas phase. With a strong focus on sustainability, this approach reduces costs and minimizes effluent production in synthesis research, promoting the eco-friendly development of new sunscreen active ingredients. METHODS: The SPARTAN'20 program was utilized for the geometry optimization and energy calculations of all compounds. Conformer distribution analysis was performed using the Merck molecular force field 94 (MMFF94), and geometry optimization was carried out using the parametric method 6 (PM6) followed by density functional theory (DFT/B3LYP/6-31G(d)). The antioxidant behavior of the hybrid compounds (I-VIII) was determined using the highest occupied molecular orbital (εHOMO) and the lowest unoccupied molecular orbital (εLUMO) energies, as well as the bond dissociation enthalpy (BDE), ionization potential (IP), and proton dissociation enthalpy (PDE) values, all calculated at the same level of structural optimization. TD-DFT study is carried out to calculate the excitation energy using the B3LYP functional with the 6-31G(d) basis set. The calculated transitions were convoluted with a Gaussian profile using the Gabedit program.

Dysregulated microRNAs in type 2 diabetes and breast cancer: Potential associated molecular mechanisms.

Type 2 diabetes (T2D) is a multifaceted and heterogeneous syndrome associated with complications such as hypertension, coronary artery disease, and notably, breast cancer (BC). The connection between T2D and BC is established through processes that involve insulin resistance, inflammation and other factors. Despite this comprehension the specific cellular and molecular mechanisms linking T2D to BC, especially through microRNAs (miRNAs), remain elusive. miRNAs are regulators of gene expression at the post-transcriptional level and have the function of regulating target genes by modulating various signaling pathways and biological processes. However, the signaling pathways and biological processes regulated by miRNAs that are associated with T2D and BC have not yet been elucidated. This review aims to identify dysregulated miRNAs in both T2D and BC, exploring potential signaling pathways and biological processes that collectively contribute to the development of BC.

Effects of passive cycling on cerebrovascular reactivity in acute brain injured patients: A pilot study.

INTRODUCTION: Early mobilization benefits critically ill patients, but concerns persist, especially in neurologic intensive care unit patients with acute brain injuries. This study assesses early mobility's impact on cerebrovascular autoregulation (CA) and systemic hemodynamics. METHODS: This single-center retrospective study focused on adult neurologic intensive care unit patients undergoing passive cycle ergometry. Data were collected from December 2020 to April 2022. Physical therapists conducted sessions using a standardized protocol, monitoring mean arterial blood pressure (MAP) and intracranial pressure (ICP). The Pressure Reactivity Index (PRx) was calculated as a measure of CA. Statistical analysis included mixed models and repeated measures ANOVA. RESULTS: Eleven patients undergoing continuous physiologic monitoring and early mobility were included, primarily with subarachnoid hemorrhage or intracranial hemorrhage. Median time to protocol initiation was 4 days, with two patients discontinuing due to hemodynamic disturbances. Over a total of 11-hours of neuromonitoring data, passive cycling demonstrated a significant reduction in heart rate (HR), MAP, and ICP across different rotations per minute (RPM) settings compared to baseline. No significant alterations in PRx or cerebral perfusion pressure (CPP) were noted at various RPM levels. However, a significant difference in PRx emerged between patients who completed the protocol and those who did not, particularly at 10 RPM. DISCUSSION: This study offers preliminary insights into the impact of early mobility on CA in acute brain injured patients. While passive cycling demonstrates promise in preserving cerebral hemodynamics, its tolerability may not be uniform across all brain-injured patients. These findings highlight the need to determine optimal early mobilization timing and intensity in this population, emphasizing the necessity for larger prospective studies to validate these findings and inform clinical practice. DETAILS: This manuscript complies with all instructions to the authors. All coauthors meet the authorship requirements and have reviewed and approved the contents of the manuscript. The manuscript has not been published totally or partly, accepted for publication, or under editorial review for publication elsewhere. We have no conflicts of interest to disclose. STROBE checklist was reviewed prior to the submission of this paper. The manuscript adheres to ethical guidelines and was approved by Cleveland Clinic's institutional research board for retrospective study. There is no funding to disclose for this study.

Enhanced Diagnostic Precision: Assessing Tumor Differentiation in Head and Neck Squamous Cell Carcinoma Using Multi-Slice Spiral CT Texture Analysis.

This study explores the efficacy of texture analysis by using preoperative multi-slice spiral computed tomography (MSCT) to non-invasively determine the grade of cellular differentiation in head and neck squamous cell carcinoma (HNSCC). In a retrospective study, MSCT scans of patients with HNSCC were analyzed and classified based on its histological grade as moderately differentiated, well-differentiated, or poorly differentiated. The location of the tumor was categorized as either in the bone or in soft tissues. Segmentation of the lesion areas was conducted, followed by texture analysis. Eleven GLCM parameters across five different distances were calculated. Median values and correlations of texture parameters were examined in relation to tumor differentiation grade by using Spearman's correlation coefficient and Kruskal-Wallis and Dunn tests. Forty-six patients were included, predominantly female (87%), with a mean age of 66.7 years. Texture analysis revealed significant parameter correlations with histopathological grades of tumor differentiation. The study identified no significant age correlation with tumor differentiation, which underscores the potential of texture analysis as an age-independent biomarker. The strong correlations between texture parameters and histopathological grades support the integration of this technique into the clinical decision-making process.

Mitigation of Subsequent Ovariectomy Responses through Prior Exercise Training in Rats.

It is well known that cardiometabolic dysfunction gradually increases after menopause, and the sedentary lifestyle can aggravate this condition. Therefore, we compared the effects of aerobic exercise training during the premenopausal period and after ovariectomy (OVX) on metabolic, hemodynamic, and autonomic parameters in an experimental rat model of menopause. The female rats were divided into four groups: control (C), sedentary OVX (SO), trained OVX (TO), and previously trained OVX (PTO). The PTO group was trained for 4 weeks prior to+8 weeks after OVX, and the TO group trained only after OVX on a motor treadmill. Autonomic modulation was evaluated, white adipose tissue (WAT) was removed and weighed, and lipolysis was assessed. The citrate synthase activity in the soleus muscle was analyzed. The trained groups prevented the impairment of baroreceptor reflex sensitivity in relation to SO; however, only PTO reduced the low-frequency band of the pulse interval compared to SO. PTO reduced the weight of WAT compared to the other groups; lipolysis in PTO was similar to that in C. PTO preserved muscle metabolic injury in all types of fibers analyzed. In conclusion, this study suggests that exercise training should be recommended in a premenopausal model to prevent cardiometabolic and autonomic menopause-induced deleterious effects.

Listeria monocytogenes from Food Products and Food Associated Environments: Antimicrobial Resistance, Genetic Clustering and Biofilm Insights.

Listeria monocytogenes, a foodborne pathogen, exhibits high adaptability to adverse environmental conditions and is common in the food industry, especially in ready-to-eat foods. L. monocytogenes strains pose food safety challenges due to their ability to form biofilms, increased resistance to disinfectants, and long-term persistence in the environment. The aim of this study was to evaluate the presence and genetic diversity of L. monocytogenes in food and related environmental products collected from 2014 to 2022 and assess antibiotic susceptibility and biofilm formation abilities. L. monocytogenes was identified in 13 out of the 227 (6%) of samples, 7 from food products (meat preparation, cheeses, and raw milk) and 6 from food-processing environments (slaughterhouse-floor and catering establishments). All isolates exhibited high biofilm-forming capacity and antibiotic susceptibility testing showed resistance to several classes of antibiotics, especially trimethoprim-sulfamethoxazole and erythromycin. Genotyping and core-genome clustering identified eight sequence types and a cluster of three very closely related ST3 isolates (all from food), suggesting a common contamination source. Whole-genome sequencing (WGS) analysis revealed resistance genes conferring resistance to fosfomycin (fosX), lincosamides (lin), fluoroquinolones (norB), and tetracycline (tetM). In addition, the qacJ gene was also detected, conferring resistance to disinfecting agents and antiseptics. Virulence gene profiling revealed the presence of 92 associated genes associated with pathogenicity, adherence, and persistence. These findings underscore the presence of L. monocytogenes strains in food products and food-associated environments, demonstrating a high virulence of these strains associated with resistance genes to antibiotics, but also to disinfectants and antiseptics. Moreover, they emphasize the need for continuous surveillance, effective risk assessment, and rigorous control measures to minimize the public health risks associated to severe infections, particularly listeriosis outbreaks. A better understanding of the complex dynamics of pathogens in food products and their associated environments can help improve overall food safety and develop more effective strategies to prevent severe health consequences and economic losses.

Effect of odontoplasty on intake, nutrient digestibility, and intake time of tifton hay in ponies.

We aimed to evaluate the effects of dental correction on voluntary nutrient intake, time of intake, apparent digestibility and fecal particle size in Brazilian ponies. Twelve mares, with no history of previous dental treatments, housed in individual pens and fed a diet based on tifton 85 were used. The study comprised two consecutive experimental phases, pre and post dental treatment. Each phase consisted of 15 days for adaptation to the pen and treatment and 5 days for data collection, totaling 20 days. To calculate nutrient intake and digestibility coefficients, samples of diets, leftovers, and feces were analyzed for dry matter (DM), crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF), crude fat (CF), mineral matter (MM), organic matter (OM), and non-fiber carbohydrates (NFC). Food intake time was recorded using a digital video recorder. Fecal particles were analyzed by wet sieving. Dental correction did not influence the intake of DM, CP, NDF, CF, and OM by the animals. However, there was an increase in NFC intake from 0.12 kg to 0.14 kg and in food intake time from 654.50 ± 138.98 to 774.95 ± 167.14. There was a decrease in the digestibility of CP from 0.08 kg to 0.04 kg and an increase in the digestibility of NDF from 0.65 kg to 0.82 kg. Although odontoplasty increased the time of hay intake and the digestibility of the fibrous fractions of the feed of ponies, it did not influence the intake of nutrients and the size of the fecal particles.

INSaFLU-TELEVIR: an open web-based bioinformatics suite for viral metagenomic detection and routine genomic surveillance.

BACKGROUND: Implementation of clinical metagenomics and pathogen genomic surveillance can be particularly challenging due to the lack of bioinformatics tools and/or expertise. In order to face this challenge, we have previously developed INSaFLU, a free web-based bioinformatics platform for virus next-generation sequencing data analysis. Here, we considerably expanded its genomic surveillance component and developed a new module (TELEVIR) for metagenomic virus identification. RESULTS: The routine genomic surveillance component was strengthened with new workflows and functionalities, including (i) a reference-based genome assembly pipeline for Oxford Nanopore technologies (ONT) data; (ii) automated SARS-CoV-2 lineage classification; (iii) Nextclade analysis; (iv) Nextstrain phylogeographic and temporal analysis (SARS-CoV-2, human and avian influenza, monkeypox, respiratory syncytial virus (RSV A/B), as well as a "generic" build for other viruses); and (v) algn2pheno for screening mutations of interest. Both INSaFLU pipelines for reference-based consensus generation (Illumina and ONT) were benchmarked against commonly used command line bioinformatics workflows for SARS-CoV-2, and an INSaFLU snakemake version was released. In parallel, a new module (TELEVIR) for virus detection was developed, after extensive benchmarking of state-of-the-art metagenomics software and following up-to-date recommendations and practices in the field. TELEVIR allows running complex workflows, covering several combinations of steps (e.g., with/without viral enrichment or host depletion), classification software (e.g., Kaiju, Kraken2, Centrifuge, FastViromeExplorer), and databases (RefSeq viral genome, Virosaurus, etc.), while culminating in user- and diagnosis-oriented reports. Finally, to potentiate real-time virus detection during ONT runs, we developed findONTime, a tool aimed at reducing costs and the time between sample reception and diagnosis. CONCLUSIONS: The accessibility, versatility, and functionality of INSaFLU-TELEVIR are expected to supply public and animal health laboratories and researchers with a user-oriented and pan-viral bioinformatics framework that promotes a strengthened and timely viral metagenomic detection and routine genomics surveillance. INSaFLU-TELEVIR is compatible with Illumina, Ion Torrent, and ONT data and is freely available at https://insaflu.insa.pt/ (online tool) and https://github.com/INSaFLU (code).

Olive mill wastewater treatment strategies to obtain quality water for irrigation: A review.

The olive mill industry is a relevant sector in the economy of Mediterranean countries, while it involves high consumption of water and the production of effluents with high environmental impact. The efficient treatment of olive mill wastewater (OMW) is of high relevance, particularly for these countries. Climate changes are leading to increasing periods of droughts, and water recovery from polluted streams is essential to ensure the sustainability of this scarce resource. A combination of various technologies involving physical, chemical, and biological processes has been developed for OMW treatment. However, the treatments studied have limitations such as the operation costs, difficulty of industrial scale-up, and the fact that the vast majority do not lead to suitable treated water for discharge/reuse. As such, it is urgent to develop a solution capable of efficiently treating this effluent, overcoming the disadvantages of existing processes to convert OMW from a serious environmental problem into a valuable source of water and nutrients. In this review, several studies based on the OMW treatment are critically discussed, from conventional approaches such as the physical (e.g. centrifugation, filtration, and adsorption) and biological (anaerobic digestion and anaerobic co-digestion) processes, to the most recent technologies such as advanced membrane filtration, advanced oxidation processes (AOPs) and sulfate radical based AOPs (SR-AOPs). Due to the complexity of the effluent, OMW cannot be efficiently treated by a single process, requiring a sequence of technologies before reaching the required characteristics for discharge into water courses or use in crop irrigation. Reviewing the published results in this matter, it seems that the sequence of processes encompassing ozonation, anaerobic digestion, and SR-AOPs could be the ideal combination for this purpose. However, membrane technologies may be necessary in the final stage of treatment so that the effluent meets legal discharge or irrigation limits.

Preservation or removal of the lateral nasal wall in endoscopic management of maxillary sinus neoplasia: A comparison of approach related morbidity.

BACKGROUND: The endoscopic modified medial maxillectomy (MMM) and prelacrimal approach (PLA) are two routinely performed endoscopic approaches to the maxillary sinus when access via a middle meatal antrostomy is insufficient. However, there is no data in the literature that has compared outcomes and complication profile between the two procedures to determine which approach is superior. OBJECTIVE: To compare the approach related morbidity of PLA and MMM. METHODS: A retrospective cohort study of all consecutive adult patients undergoing either MMM or PLA from 2009 to 2023 were identified. The primary outcome was development of epistaxis, paraesthesia, lacrimal injury, iatrogenic sinus dysfunction within a minimum of 3 months post-operative follow up. RESULTS: 39 patients (44 sides) underwent PLA and 96 (96 sides) underwent MMM. There were no statistically significant differences between the rates of paraesthesia (9.1 % vs 14.6 %, p = 0.367) or prolonged paraesthesia (2.3 % vs 5.2 %, p = 0.426), iatrogenic maxillary sinus dysfunction (2.3 % vs 5.2 %, p = 0.426) or adhesions requiring removal (4.5 % vs 4.2 %, p = 0.918). No cases of epiphora or nasal cavity stenosis occurred in either arm in our study. CONCLUSIONS: According to our data, the endoscopic modified medial maxillectomy and prelacrimal approach are both equally safe approaches with their own benefits to access.

Forensic psychological procedures in cases of technology-facilitated sexual abuse among adolescents: A scoping review.

Technology-facilitated sexual abuse refers to the use of information and communication technologies to facilitate both virtual and in-person sexual crimes. Research on this topic has focused on rates, risk factors, and consequences. This scoping review aims to understand whether and how forensic psychological procedures are adapted to assess adolescent victims and how Internet-based information might be useful as complementary data. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extensions for Scoping Reviews guidelines, searches were conducted in April 2023 in five electronic databases to include Portuguese, Spanish, or English quantitative, qualitative, or mixed-method peer-reviewed studies. Of the 2523 studies, six were considered eligible. Identified procedures include forensic interviews following the National Institute for Child Health and Human Development Protocol, and risk and trauma assessments. While discussing technology's role in abuse during interviews was informative, confronting adolescents with evidence of their abuse had adverse effects on their testimony and recovery. The assessment tools often had a narrow focus or overlooked the abuse unless explicitly disclosed, implied a referral, or when safeguarding concerns were raised. Clinical, forensic, and criminal implications are elaborated.

Unveiling a Listeria monocytogenes Outbreak in a Rabbit Farm: Clinical Manifestation, Antimicrobial Resistance, Genomic Insights and Environmental Investigation.

Listeria monocytogenes poses a threat to both human and animal health. This work describes an L. monocytogenes outbreak in a Portuguese rabbit farm, detailing the isolates' clinical manifestations, necropsy findings, and phenotypic and genomic profiles. Clinical signs, exclusively observed in does, included lethargy and reproductive signs. Post-mortem examination of does revealed splenomegaly, hepatomegaly with a reticular pattern, pulmonary congestion, and haemorrhagic lesions in the uterus, with thickening of the uterine wall and purulent greyish exudates. Positive L. monocytogenes samples were identified in fattening and maternity units across different samples, encompassing does and environmental samples. Core-genome Multi Locus Sequence Typing (cgMLST) analysis confirmed the outbreak, with the 16 sequenced isolates (lineage II, CC31, and ST325) clustering within a ≤2 allelic difference (AD) threshold. Antimicrobial susceptibility testing for five antibiotics revealed that 15 out of 19 outbreak isolates were resistant to sulfamethoxazole-trimethoprim (SXT). Concordantly, all SXT-resistant sequenced isolates were found to exclusively harbour a plasmid containing a trimethoprim-resistance gene (dfrD), along with loci linked to resistance to lincosamides (lnuG), macrolides (mphB), and polyether ionophores (NarAB operon). All sequenced outbreak isolates carried the antibiotic resistance-related genes tetM, fosX, lin, norB, lmrB, sul, and mprF. The outbreak cluster comprises isolates from does and the environment, which underscores the ubiquitous presence of L. monocytogenes and emphasizes the importance of biosecurity measures. Despite limited data on listeriosis in rabbit farming, this outbreak reveals its significant impact on animal welfare and production.

Recurrence, Microevolution, and Spatiotemporal Dynamics of Legionella pneumophila Sequence Type 1905, Portugal, 2014-2022.

We investigated molecular evolution and spatiotemporal dynamics of atypical Legionella pneumophila serogroup 1 sequence type 1905 and determined its long-term persistence and linkage to human disease in dispersed locations, far beyond the large 2014 outbreak epicenter in Portugal. Our finding highlights the need for public health interventions to prevent further disease spread.

Raw milk cheeses from Beira Baixa, Portugal-A contributive study for the microbiological hygiene and safety assessment.

Due to specific bacterial microbiota, raw milk cheeses have appreciated sensory properties. However, they may pose a threat to consumer safety due to potential pathogens presence. This study evaluated the microbiological contamination of 98 raw milk cheeses from Beira Baixa, Portugal. Presence and enumeration of Coagulase Positive Staphylococci (CPS), Listeria monocytogenes, Salmonella spp., pathogenic Escherichia coli, and indicator microorganisms (non-pathogenic E. coli and Listeria spp.) was attained. E. coli antimicrobial resistance (AMR) was also evaluated. PCR and/or Whole genome sequencing (WGS) was used to characterize E. coli, Salmonella spp. and L. monocytogenes isolates. Sixteen cheeses (16.3%) were classified as Satisfactory, 59 (60.2%) as Borderline and 23 (23.5%) as Unsatisfactory/Potential Injurious to Health. L. monocytogenes, CPS > 104 cfu g-1, Extraintestinal pathogenic E. coli (ExPEC) and Salmonella spp. were detected in 4.1%, 6.1%, 3.1% and 1.0% of the samples, respectively. Listeria innocua (4.1%) and E. coli > 104 cfu g-1 (16.3%) were also detected. AMR E. coli was detected in 23/98 (23.5%) of the cheese samples, of which two were multidrug resistant. WGS identified genotypes already associated to human disease and Listeria spp. cluster analysis indicated that cheese contamination might be related with noncompliance with Good Hygiene Practices during cheese production.

Trial of Early Minimally Invasive Removal of Intracerebral Hemorrhage.

BACKGROUND: Trials of surgical evacuation of supratentorial intracerebral hemorrhages have generally shown no functional benefit. Whether early minimally invasive surgical removal would result in better outcomes than medical management is not known. METHODS: In this multicenter, randomized trial involving patients with an acute intracerebral hemorrhage, we assessed surgical removal of the hematoma as compared with medical management. Patients who had a lobar or anterior basal ganglia hemorrhage with a hematoma volume of 30 to 80 ml were assigned, in a 1:1 ratio, within 24 hours after the time that they were last known to be well, to minimally invasive surgical removal of the hematoma plus guideline-based medical management (surgery group) or to guideline-based medical management alone (control group). The primary efficacy end point was the mean score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes, according to patients' assessment) at 180 days, with a prespecified threshold for posterior probability of superiority of 0.975 or higher. The trial included rules for adaptation of enrollment criteria on the basis of hemorrhage location. A primary safety end point was death within 30 days after enrollment. RESULTS: A total of 300 patients were enrolled, of whom 30.7% had anterior basal ganglia hemorrhages and 69.3% had lobar hemorrhages. After 175 patients had been enrolled, an adaptation rule was triggered, and only persons with lobar hemorrhages were enrolled. The mean score on the utility-weighted modified Rankin scale at 180 days was 0.458 in the surgery group and 0.374 in the control group (difference, 0.084; 95% Bayesian credible interval, 0.005 to 0.163; posterior probability of superiority of surgery, 0.981). The mean between-group difference was 0.127 (95% Bayesian credible interval, 0.035 to 0.219) among patients with lobar hemorrhages and -0.013 (95% Bayesian credible interval, -0.147 to 0.116) among those with anterior basal ganglia hemorrhages. The percentage of patients who had died by 30 days was 9.3% in the surgery group and 18.0% in the control group. Five patients (3.3%) in the surgery group had postoperative rebleeding and neurologic deterioration. CONCLUSIONS: Among patients in whom surgery could be performed within 24 hours after an acute intracerebral hemorrhage, minimally invasive hematoma evacuation resulted in better functional outcomes at 180 days than those with guideline-based medical management. The effect of surgery appeared to be attributable to intervention for lobar hemorrhages. (Funded by Nico; ENRICH ClinicalTrials.gov number, NCT02880878.).

Synthesis and In vitro and In silico Anti-inflammatory Activity of New Thiazolidinedione-quinoline Derivatives.

BACKGROUND: Inflammation is a series of complex defense-related reactions. The inflammation cascade produces various pro-inflammatory mediators. Unregulated production of these pro-inflammatory mediators can lead to a wide range of diseases, including rheumatoid arthritis, sepsis, and inflammatory bowel disease. In the literature, the anti-inflammatory action of quinoline and thiazolidinedione nuclei are well established, alone, and associated with other nuclei. The synthesis of hybrid molecules is a strategy for obtaining more efficient molecules due to the union of pharmacophoric nuclei known to be related to pharmacological activity. OBJECTIVES: Based on this, this work presents the synthesis of thiazolidinedione-quinoline molecular hybrids and their involvement in the modulation of cytokines involved in the inflammatory reaction cascade. METHODS: After synthesis and characterization, the compounds were submitted to cell viability test (MTT), ELISA IFN-γ and TNF-α, adipogenic differentiation, and molecular docking assay with PPARy and COX-2 targets. RESULTS: LPSF/ZKD2 and LPSF/ZKD7 showed a significant decrease in the concentration of IFN- γ and TNF-α, with a dose-dependent behavior. LPSF/ZKD4 at a concentration of 50 µM significantly reduced IL-6 expression. LPSF/ZKD4 demonstrates lipid accumulation with significant differences between the untreated and negative control groups, indicating a relevant agonist action on the PPARγ receptor. Molecular docking showed that all synthesized compounds have good affinity with PPARγ e COX-2, with binding energy close to -10,000 Kcal/mol. CONCLUSION: These results demonstrate that the synthesis of quinoline-thiazolidinedione hybrids may be a useful strategy for obtaining promising candidates for new anti-inflammatory agents.