Ocular pharmacokinetics of acetazolamide from intravitreal implants by high-performance liquid chromatography coupled to tandem mass spectrometry.

Glaucoma, a leading cause of irreversible blindness, affects about 70 million people globally. Its treatment focuses on reducing intraocular pressure. Acetazolamide, a potent anti-glaucoma drug, is currently used only systemically due to low solubility and permeation, which cause severe side effects. Developing topical medications with acetazolamide requires robust analytical methods for its detection in biological samples. In this context, this study aimed to develop a method to quantify acetazolamide in rabbit vitreous humor samples. The method involved a simple, fast, inexpensive, and environmentally friendly protein precipitation step for sample preparation, needing just 50 µL of sample and 200 µL of organic solvent, with adequate recovery. This was combined with high-performance liquid chromatography coupled to tandem mass spectrometry, enabling highly sensitive (LOQ of 5 ng/mL) quantification within only 5 min. The method proved to be selective, precise, and accurate, with well-fitted analytical curves, with no carryover, and no matrix effect impacting reliability. The method was successfully applied to analyze vitreous humor samples from rabbits in pharmacokinetic studies, monitoring drug release from intravitreal implants. Results showed a controlled release profile, with a maximum drug concentration (Cmax) of 426.01 ± 64.57 ng/mL, time to reach Cmax (Tmax) of 28 days, and area under the curve (AUC0-42 and AUC0-∞) of 7722.66 ± 1125.96 ng days/mL and 8998.11 ± 1311.92 ng days/mL, respectively. The device demonstrated significantly slower elimination, ensuring therapeutic levels for an extended period when compared to intravitreal injection.

Diathermy Versus Scalpel in Midline Abdominal Incision: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Our study aimed to compare the midline abdominal incision with scalpel and diathermy. METHODS: PubMed, EMBASE, and Cochrane were searched through January 2024 following PRISMA guidelines (PROSPERO, ID: CRD42024516771), and only randomized controlled trials were included. Heterogeneity was assessed using Cochran's Q test and the I2 heterogeneity index. Statistical analysis was performed using Review Manager 5.4 software. RESULTS: Six randomized controlled trials were included, from which 469 patients (51.5%) received diathermy incision and 442 patients (48.5%) underwent the scalpel technique. Patients treated with the electrocautery approach had less incision blood loss (MD -17.57 mL; P < .01). No statistically significant differences were found between groups regarding wound infection incidence, incision time, incision area or first-day postoperative pain. CONCLUSION: Diathermy use in midline abdominal incision may be advocated as it demonstrated a significant reduction in incision-related blood loss, with no differences in wound infection or early postoperative pain incidences compared to the scalpel.

Endoscopic submucosal dissection vs. endoscopic mucosal resection in the treatment of early Barrett's neoplasia: Systematic review and meta-analysis.

OBJECTIVES: Endoscopic resection is the preferred approach to treat early Barrett's neoplasia, reducing the need for surgical interventions. However, the best choice between endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) remains unclear. The study aimed to compare the efficacy and safety of EMR vs. ESD for early Barrett's neoplasia. METHODS: An electronic search was conducted in MEDLINE, Central Cochrane, EMBASE, and LILACS until November 2023. Studies comparing ESD vs. EMR in the treatment of patients with early Barrett's neoplasia were included. This study was performed according to the Preferred Report Items for Systematic Reviews and Meta-Analyses guidelines. The ROBIN-I tool was used to analyze the risk of bias and GRADE to measure the quality of the evidence. RESULTS: A total of 9352 patients from 15 observational studies were included. Patients undergoing ESD had significantly higher rates of en-bloc (odds ratio [OR] 25.96, 95% confidence interval [CI] 13.82, 48.74; I2 = 52%; P < 0.00001) and R0 (OR 5.10, 95% CI 3.29, 7.91; I2 = 73%; P < 0.00001) with a higher risk of adverse events, including bleeding, stricture formation, and perforation. In a subgroup analysis of patients who did not receive radiofrequency ablation, ESD had a lower recurrence rate than EMR (OR 0.22, 95% CI 0.05, 0.94; I2 = 88%; P = 0.04). CONCLUSION: Endoscopic submucosal dissection is more effective than EMR in treating early Barrett's neoplasia at the expense of higher adverse events rates.

Patient-Related Factors Associated With Long-Term Outcomes After Successful Endoscopic Balloon Dilation For Crohn's Disease-Associated Ileo-Colic Strictures: A Systematic Review and Meta-analysis.

Background: Successful Crohn's disease (CD) therapy relies on timely and precise management strategies. Endoscopic balloon dilation (EBD) has been applied as a first-line treatment for symptomatic CD-associated strictures due to its minimally invasive nature and the possibility of preserving intestinal length. Objective: The aim of the present study was to determine patient-related predictive factors associated with the need for surgery for CD-associated ileocolic strictures after technically successful EBD. Methods: All original studies published before December 2023 that reported the outcomes of patients treated with EBD for ileocolic strictures secondary to CD and described follow-up for at least 1 year were included. The difference in risk of needing surgery was calculated for 8 different patient characteristics (Sex, smoking habit, previous surgery, biologic therapy, steroids, immunosuppressors, nature of the stricture, and endoscopic disease activity). Results: There were significant differences in the risk of needing surgery after EBD among patients who underwent surgery and patients without a history of surgery (RD: -0.20 [-0.31, -0.08]), patients with endoscopic mucosal activity and patients in remission at the time of EBD (RD: 0.19 [0.04, 0.34]), patients using biologics at the time of EBD and patients not using biologics (RD: -0.09 [-0.16, -0.03]), and patients using steroids and those not using steroids at the time of EBD (RD: 0.16 [0.07, 0.26]). Conclusions: The use of biologics and endoscopic disease remission at the time of EBD were protective factors against the need for surgery. No previous surgery or use of steroids at the time of EBD was associated with the need for surgery during follow-up.

Diffusion tensor metrics, motor and non-motor symptoms in de novo Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurons' degeneration of the substantia nigra, presenting with motor and non-motor symptoms. We hypothesized that altered diffusion metrics are associated with clinical symptoms in de novo PD patients. METHODS: Fractional Anisotropy (FA) and Mean (MD), Axial (AD), and Radial Diffusivity (RD) were assessed in 55 de novo PD patients (58.62 ± 9.85 years, 37 men) and 55 age-matched healthy controls (59.92 ± 11.25 years, 34 men). Diffusion-weighted images and clinical variables were collected from the Parkinson's Progression Markers Initiative study. Tract-based spatial statistics were used to identify white matter (WM) changes, and fiber tracts were localized using the JHU-WM tractography atlas. Motor and non-motor symptoms were evaluated in patients. RESULTS: We observed higher FA values and lower RD values in patients than controls in various fiber tracts (p-TFCE < 0.05). No significant MD or AD difference was observed between groups. Diffusion metrics of several regions significantly correlated with non-motor (state and trait anxiety and daytime sleepiness) and axial motor symptoms in the de novo PD group. No correlations were observed between diffusion metrics and other clinical symptoms evaluated. CONCLUSION: Our findings suggest microstructural changes in de novo PD fiber tracts; however, limited associations with clinical symptoms reveal the complexity of PD pathology. They may contribute to understanding the neurobiological changes underlying PD and have implications for developing targeted interventions. However, further longitudinal research with larger cohorts and consideration of confounding factors are necessary to elucidate the underlying mechanisms of these diffusion alterations in de novo PD.

Baseline brain volume predicts home-based transcranial direct current stimulation effects on inattention in adults with attention-deficit/hyperactivity disorder.

BACKGROUND: Home-based transcranial direct current stimulation (Hb-tDCS) is a non-invasive brain stimulation technique that utilizes low-intensity electric currents delivered via scalp electrodes to modulate brain activity. It holds significant promise for addressing inattention in adults with attention-deficit/hyperactivity disorder (ADHD). However, its effectiveness varies among individuals, and predicting outcomes remains uncertain, partially due to the influence of individual differences in ADHD-related brain anatomy. METHODS: We analyzed data from a subsample, composed by twenty-nine adult patients with ADHD, of the Treatment of Inattention Symptoms in Adult Patients with ADHD (TUNED) trial. Fourteen patients underwent active anodal right cathodal left dorsolateral prefrontal cortex (DLPFC) Hb-tDCS for 4 weeks and fifteen received sham-related tDCS intervention. Inattention outcome was evaluated at both baseline and endpoint (4th week). Baseline structural measures of the DLPFC, anterior cingulate cortex (ACC) and subcortical structures, previously associated with ADHD, were quantified. Several linear mixed models, with a three-way interaction between the fixed predictors brain volume or thickness, time, and treatment were calculated. Multiple comparison corrections were applied using the Benjamini-Hochberg method. RESULTS: Baseline volume of the left DLPFC regions middle frontal gyrus (t (25) = 3.33, p-adjusted = 0.045, Cohen's d = 1.33, 95% CI = [0.45, 2.19]), inferior frontal gyrus (orbital part) (t (25) = 3.10, p-adjusted = 0.045, Cohen's d = 1.24, 95% CI = [0.37, 2.08]), and of the left ACC supragenual (t (25) = 3.15, p-adjusted = 0.045, Cohen's d = 1.26, 95% CI = [0.39, 2.11]) presented significant association with the inattentive score improvement only in the active tDCS group. More specifically, the smaller these regions were, the more the symptoms improved following anodal right cathodal left DLPFC Hb-tDCS. CONCLUSION: Hb-tDCS was associated with greater improvement in brain areas related to attention regulation. Brain MRI can be potentially used to predict clinical response to tDCS in ADHD adults.

Impact of an Exercise-Based Cardiac Rehabilitation Program on Cardiopulmonary Test Parameters.

INTRODUCTION: Exercise-based cardiac rehabilitation programs (CRPs) represent a multidisciplinary therapeutic approach tailored to improve cardiorespiratory fitness and overall health-related quality of life, while reducing cardiovascular hospitalizations and mortality. Our aim was to determine changes in exercise capacity and cardiac events according to the left ventricular ejection fraction (LVEF) following a CRP. METHODS: This single-center cohort study included 131 patients who completed a center-based CRP from 2015 to 2022. Cardiopulmonary exercise testing (CPET), transthoracic echocardiography, and laboratory analysis were performed before and after program completion. RESULTS: Of 232 enrolled patients, 131 were included in our cohort analysis, with 36.6% having a reduced LVEF. These patients exhibited higher rates of atrial fibrillation (p = 0.019) and NT-proBNP values (p < 0.001). Patients with reduced LVEF had lower peak VO2 (pVO2) (p = 0.046), percentage of predicted oxygen consumption (ppVO2) (p < 0.001), and VO2 at anaerobic threshold (p = 0.015) during baseline CPET. Completion of the CRP led to comparable improvements in exercise performance between groups, assessed through Δ pVO2 (p = 0.990), Δ ppVO2 (p = 0.610), and Δ VE/VCO2 slope (p = 0.200). In the study population, male gender and hypertension independently predicted variation in VE/VCO2 slope (p = 0.017) and oxygen uptake efficiency slope (p = 0.048), respectively, post-CRP. During follow-up, 9.2% of all patients had hospital admissions for cardiac events, and 3.8% died, with no significant differences between groups. CONCLUSION: Patients with reduced LVEF admitted to our CRP showed lower functional status based on specific CPET parameters. After CRP, both reduced and preserved LVEF groups experienced similar functional improvements. Therefore, strategies to increase participation of patients with reduced LVEF in such programs are warranted.

Combined effects of high hydrostatic pressure and pulsed electric fields on quinoa starch: Analysis of microstructure, morphology, thermal, and pasting properties.

The aim of this study was to evaluate the impact of non-thermal methods, using high hydrostatic pressure (HHP) and pulsed electric field (PEF), on the dual modification of quinoa starch and to analyze the microstructural, morphological, thermal, pasting, and texture properties. Starch was treated with HHP at 400 MPa for 10 min, while PEF was applied using voltages of 10 and 30 kV cm-1 for a total time of 90s. The modification techniques were effective in breaking down amylose molecules and amylopectin branches, where for the dual treatment, higher values of DP6-12 were found. The average diameter and gelatinization temperatures were elevated after HHP, thus forming clusters that require more energy for paste formation. The use of 30 kV cm-1 and 400 MPa (HP30) in starch facilitates the creation of new food products with better texture, stability and nutritional value, making them suitable for use in food emulsions and the cosmetics industry.

Pediatric suicide attempts lagged during the COVID-19 pandemic: a European multicenter study.

BACKGROUND: Elevated rates of suicidal behavior were reported during the COVID-19 pandemic. However, information is scarce on patients' profiles during this period. Studies evoke the potential adverse effects of the mandatory lockdown, but they remain relatively speculative. METHODS: We monitored fluctuations in suicide attempts (SA) in six European countries. We gathered data, retrospectively for under 18-year-old SA episodes (1 January 2018 to 31 December 2021), through records of psychiatric emergency services. We collected clinical profiles individually. We extracted environmental indicators by month, as provided by Oxford COVID-19 Government Response Tracker (OxCGRT). We used the Pruned Exact Linear Time (PELT) method to identify breakpoints in SA episodes reported for each country, and logistic regressions to estimate changes in patients' characteristics after the breakpoints. Finally, we used a univariate and multivariate negative binomial model to assess the link between SA and OxCGRT indicators, accounting for the delay (lag) between the interventions and their impact on SA. RESULTS: The study comprised 2,833 children and adolescents (mean age = 15.1 years (SD 1.6); M: F sex-ratio = 1:5.4). A significant increase in SA was found either 6 or 10 months after the beginning of the pandemic, varying by country. Patients were more likely to be girls (aOR = 1.77 [1.34; 2.34]) and used SA methods "other than self-poisoning" (aOR = 1.34 [1.05; 1.7]). In the multivariate model, an association was found between SA and the contact tracing indicator with an 11 months delay, and the number of COVID-19 deaths with a 3-months delay. CONCLUSIONS: Findings confirmed a delayed increase in SA during the COVID-19 pandemic in children and adolescents as well as changes in patients' profiles. The duration and severity of the pandemic emerged as the strongest predictor in the rise of SA. If faced with a similar pandemic in the future, the gap between the onset of pandemic and the increase in suicide attempts presents an opportunity for prevention.

High expression of PD-L1 on conventional dendritic cells in tumour-draining lymph nodes is associated with poor prognosis in oral cancer.

INTRODUCTION: Oral squamous cell carcinoma (OSCC), while common and with a favorable prognosis in early stages, presents a marked reduction in survival rate upon metastasis to lymph nodes. Early detection of lymph node metastasis via biomarkers could enhance the therapeutic strategy for OSCC. Here, we explored dendritic cells (DCs) and cytotoxic T-cells in tumour-draining lymph nodes (TDLNs) as potential biomarkers. METHOD: Dendritic cells and cytotoxic T-cells in 33 lymph nodes were analyzed with multi-parameter flow cytometry in TDLNs, regional non-TDLNs surgically excised from 12 OSCC patients, and compared to 9 lymph nodes from patients with benign conditions. RESULTS: Our results displayed a higher proportion of conventional cDC1s with immunosuppressive features in TDLN. Further, high PD-L1 expression on cDC1 in TDLNs was associated with metastasis and/or recurrent disease risk. Also, elevated levels of memory CD8+ T-cells and terminally exhausted PD-1+TCF-1-CD8+ T-cells were observed in TDLNs and non-TDLNs compared to healthy lymph nodes. CONCLUSIONS: We conclude that TDLNs contain cells that could trigger an anti-tumor adaptive response, as evidenced by activated cDC1s and progenitor-like TCF-1+ T-cells. The detection of high PDL1 expression on cDC1s was indicative of TDLN metastasis and an adverse prognosis, proposing that PD-L1 on dendritic cells in TDLN could serve as a predictive biomarker of OSCC patients with a worse prognosis.

Antinociceptive and anti-inflammatory activities of Ayapana triplinervis essential oil rich in thymohydroquinone dimethyl ether from Brazil.

Ayapana triplinervis (M.Vahl) R.M.King & H.Rob. (Asteraceae), popularly known as japana, is a tropical, aromatic subshrub widely used as tea to combat some diseases. The essential oil was obtained from the leaves by hydrodistillation (3 h), and the chemical composition was analyzed by gas chromatography coupled to mass spectrometry. For in vivo assays, Mus musculus/Swiss mice were used to evaluate oral acute toxicological (at dose of 2000 mg/kg); peripheral and central analgesic for abdominal contortion (doses of 6.25, 12.5, 25, 50 and 100 mg/kg), hot plate test (12.5, 25, 50, and 100 mg/kg) and formalin (25, 50 and 100 mg/kg); open field test (100 mg/kg); and anti-inflammatory by ear swelling induced by xylene (6.25,12.5, 25, 50, and 100 mg/kg). The yield of A. triplinervis essential oil (AtEO) was 4.6%, and the oxygenated monoterpene 2,5-dimethoxy-p-cymene was the major compound in this study (63.6%). AtEO at a dose of 2,000 mg/kg orally did not change the behavior patterns or mortality of the animals; liver and kidney biochemical levels were similar to the control group, indicating no liver and kidney toxicity. Moreover, AtEO, at doses of 6.25, 12.5, 25, 50, and 100 mg/kg, reduced abdominal contortions by 21%, 54%, 91%, 58%, and 55%, respectively. In the hot plate test, AtEO showed a significant increase in latency time in the 60-min interval at doses of 25 mg/kg (11.3 ± 3.3 s) and 100 mg/kg (11.9 ± 0.9 s). In the first phase of the formalin test, AtEO decreased paw licking time at doses of 25, 50, and 100 mg/kg, with inhibition of 22%, 38%, and 83%; in the second phase, the same doses, decreased licking time with inhibition of 24%, 34%, and 76%. AtEO did not present a significant change in the spontaneous locomotor activity of the animals. Doses of 6.25, 12.5, 25, 50, and 100 mg/kg significantly reduced ear edema induced by topical application of xylene with percentages of 40%, 39%, 54%, 45%, and 45%, respectively. So, AtEO demonstrated low acute oral toxicity and exhibited significant antinociceptive and anti-inflammatory actions, consistent with the use of A. triplinervis in traditional medicine.

Pulmonary arterial hypertension: Navigating the pathways of progress in diagnosis, treatment, and patient care.

Pulmonary arterial hypertension (PAH) is a form of precapillary pulmonary hypertension caused by a complex process of endothelial dysfunction and vascular remodeling. If left untreated, this progressive disease presents with symptoms of incapacitating fatigue causing marked loss of quality of life, eventually culminating in right ventricular failure and death. Patient management is complex and based on accurate diagnosis, risk stratification, and treatment initiation, with close monitoring of response and disease progression. Understanding the underlying pathophysiology has enabled the development of multiple drugs directed at different targets in the pathological chain. Vasodilator therapy has been the mainstay approach for the last few years, significantly improving quality of life, functional status, and survival. Recent advances in therapies targeting dysfunctional pathways beyond endothelial dysfunction may address the fundamental processes underlying the disease, raising the prospect of increasingly effective options for this high-risk group of patients with a historically poor prognosis.

Payment perception in the emergency department: The mediating role of perceived quality of healthcare and patient satisfaction.

The aim of this research is to identify the main factors associated with patients' payment perception and the effects of these factors on payment perception. Patients admitted between January and December 2016 at an emergency department of a public hospital in Lisbon, Portugal, were included in this study, with a representative sample size of 382 patients. A 5% margin of error and a 95% confidence interval were used, and all the data were collected between May and November 2017. To test the mediation models, stepwise multiple linear regression analysis was used. The effect of doctors on payment perception through satisfaction and through perceived quality of healthcare (PQHC) is explained by 3% and 4% of the variation, respectively, with statistically significant results (P < .01). Moreover, the effect of privacy and meeting expectations on payment perception through PQHC is explained by 4% and 4% of the variation, with statistically significant results (P < .01). Doctors play a crucial role in understanding the patients' payment perception (with direct and indirect effects). Mediators, in turn, strengthen this effect, in which the contribution of PQHC is more significant than that of satisfaction.

Functional and Effective Connectivity Underlying Semantic Verbal Fluency.

Semantic verbal fluency (SVF) impairment is present in several neurological disorders. Although activation in SVF-related areas has been reported, how these regions are connected and their functional roles in the network remain divergent. We assessed SVF static and dynamic functional connectivity (FC) and effective connectivity in healthy participants using functional magnetic resonance imaging. We observed activation in the inferior frontal (IFG), middle temporal (pMTG) and angular gyri (AG), anterior cingulate (AC), insular cortex, and regions of the superior, middle, and medial frontal gyri (SFG, MFG, MidFG). Our static FC analysis showed a highly interconnected task and resting state network. Increased connectivity of AC with the pMTG and AG was observed for the task. The dynamic FC analysis provided circuits with connections similarly modulated across time and regions related to category identification, language comprehension, word selection and recovery, word generation, inhibition of speaking, speech planning, and articulatory planning of orofacial movements. Finally, the effective connectivity analysis provided a network that best explained our data, starting at the AG and going to the pMTG, from which there was a division between the ventral and dorsal streams. The SFG and MFG regions were connected and modulated by the MidFG, while the inferior regions formed the ventral stream. Therefore, we successfully assessed the SVF network, exploring regions associated with the entire processing, from category identification to word generation. The methodological approach can be helpful for further investigation of the SVF network in neurological disorders.

Scissor-assisted vs. conventional endoscopic submucosal dissection for colorectal lesions: Systematic review and meta-analysis.

OBJECTIVES: Colorectal endoscopic submucosal dissection (ESD) is a technically complex procedure. The scissor knife mechanism may potentially provide easier and safer colorectal ESD. The aim of this meta-analysis is to evaluate the efficacy and safety of scissor-assisted vs. conventional ESD for colorectal lesions. METHODS: A search strategy was conducted in MEDLINE, Embase, and Lilacs databases from January 1990 to November 2023 according to PRISMA guidelines. Fixed and random-effects models were used for statistical analysis. Heterogeneity was assessed using I2 test. Risk of bias was assessed using the ROBINS-I and RoB-2 tools. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. RESULTS: A total of five studies (three retrospective and two randomized controlled trials, including a total of 1575 colorectal ESD) were selected. The intraoperative perforation rate was statistically lower (risk difference [RD] -0.02; 95% confidence interval [CI] -0.04 to -0.01; P = 0.001; I2 = 0%) and the self-completion rate was statistically higher (RD 0.14; 95% CI 0.06, 0.23; P = 0.0006; I2 = 0%) in the scissor-assisted group compared with the conventional ESD group. There was no statistical difference in R0 resection rate, en bloc resection rate, mean procedure time, or delayed bleeding rate between the groups. CONCLUSION: Scissor knife-assisted ESD is as effective as conventional knife-assisted ESD for colorectal lesions with lower intraoperative perforation rate and a higher self-completion rate.

Lippia alba essential oil: A powerful and valuable antinociceptive and anti-inflammatory medicinal plant from Brazil.

ETHNOPHARMACOLOGICAL RELEVANCE: In Brazilian popular medicine, Lippia alba leaves are used in teas to treat pain and inflammatory diseases. AIM OF THE STUDY: to evaluate the chemical composition, antinociceptive, and anti-inflammatory activities of Lippia alba essential oil and its major compound geraniol. MATERIAL AND METHODS: Lippia alba leaves were collected in Pará state, Brazil. The leaf essential oil was obtained using a modified Clevenger-type extractor. Then, the oil was analyzed by GC and GC-MS analyses. To evaluate the toxicity of LaEO and geraniol, the doses of 50, 300, and 2000 mg/kg were used in a mouse model. For antinociception tests, abdominal contortion, hot plate, and formalin tests were used; all groups were treated with LaEO and geraniol at doses of 25, 50, and 100 mg/kg; and to evaluate inflammation using the ear edema model. RESULTS: The constituents identified in the highest content were oxygenated monoterpenes: geraniol (37.5%), geranial (6.7%) and neral (3.8%). The animals treated with LaEO and geraniol demonstrated atypical behaviors with aspects of lethargy and drowsiness, characteristics of animals in a state of sedation; the relative weights showed no significant difference compared to the controls. In the abdominal contortion test, LaEO at 25 mg/kg, 50 mg/kg doses, and 100 mg/kg reduced the number of contortions, representing a percentage reduction of 84.64%, 81.23%, and 66.21% respectively. In the hot plate test, LaEO and geraniol increased the latency time at doses of 25, 50, and 100 mg/kg in all test periods; there was no statistical difference between LaEO and geraniol. In the first phase of the formalin test, only doses of 25 mg/kg and 100 mg/kg of LaEO showed significant activity, reducing the latency time by 53.40% and 58.90%. LaEO at doses of 25 mg/kg and 100 mg/kg reduced the size of the edema, demonstrating an anti-inflammatory activity of 59.38% (25 mg/kg) and 50% (100 mg/kg). CONCLUSION: Lippia alba essential oil and geraniol showed central/peripheral analgesic and anti-inflammatory potential and can be used as an alternative or complementary treatment to conventional drugs. More studies are needed to evaluate its action mechanisms and its analgesic effects.

Yttrium immobilization through biomineralization with phosphate by the resistant strain Mesorhizobium qingshengii J19.

AIMS: Yttrium (Y) holds significant industrial and economic importance, being listed as a critical element on the European list of critical elements, thus emphasizing the high priority for its recovery. Bacterial strategies play a crucial role in the biorecovery of metals, offering a promising and environmentally friendly approach. Therefore, gaining a comprehensive understanding of the underlying mechanisms behind bacterial resistance, as well as the processes of bioaccumulation and biotransformation, is of paramount importance. METHODS AND RESULTS: A total of 207 Alphaproteobacteria strains from the University of Coimbra Bacteria Culture Collection were tested for Y-resistance. Among these, strain Mesorhizobium qingshengii J19 exhibited high resistance (up to 4 mM Y) and remarkable Y accumulation capacity, particularly in the cell membrane. Electron microscopy revealed Y-phosphate interactions, while X-ray diffraction identified Y(PO3)3·9H2O biocrystals produced by J19 cells. CONCLUSION: This study elucidates Y immobilization through biomineralization within phosphate biocrystals using M. qingshengii J19 cells.

Coastal natural products: a review applied to antimycobacterial activity.

Despite the many advances in drug research, natural products are still being explored as a promising source for discovering new bioactive compounds to treat global diseases such as tuberculosis. However, there is a lack of studies and information about coastal natural products, which thrive in the transitional environment between two different ecosystems and produce unique secondary metabolites. Mangroves, estuaries, and mudflats make up areas for coastal species and have shown promising results in antituberculosis research, some of them are present in hotspot areas. This review focuses on research conducted in coastal environments and explores the reasons why these natural products tend to outperform non-coastal ones against the causative agent of tuberculosis, Mycobacterium tuberculosis.

Binding Evolution of the Dengue Virus Envelope Against DC-SIGN: A Combined Approach of Phylogenetics and Molecular Dynamics Analyses Over 30 Years of Dengue Virus in Brazil.

The Red Queen Hypothesis (RQH), derived from Lewis Carroll's "Through the Looking-Glass", postulates that organisms must continually adapt in response to each other to maintain relative fitness. Within the context of host-pathogen interactions, the RQH implies an evolutionary arms race, wherein viruses evolve to exploit hosts and hosts evolve to resist viral invasion. This study delves into the dynamics of the RQH in the context of virus-cell interactions, specifically focusing on virus receptors and cell receptors. We observed multiple virus-host systems and noted patterns of co-evolution. As viruses evolved receptor-binding proteins to effectively engage with cell receptors, cells countered by altering their receptor genes. This ongoing mutual adaptation cycle has influenced the molecular intricacies of receptor-ligand interactions. Our data supports the RQH as a driving force behind the diversification and specialization of both viral and host cell receptors. Understanding this co-evolutionary dance offers insights into the unpredictability of emerging viral diseases and potential therapeutic interventions. Future research is crucial to dissect the nuanced molecular changes and the broader ecological consequences of this ever-evolving battle. Here, we combine phylogenetic inferences, structural modeling, and molecular dynamics analyses to describe the epidemiological characteristics of major Brazilian DENV strains that circulated from 1990 to 2022 from a combined perspective, thus providing us with a more detailed picture on the dynamics of such interactions over time.

Detection of Mtb and NTM: preclinical validation of a new asymmetric PCR-binary deoxyribozyme sensor assay.

Tuberculosis (TB) and infectious diseases caused by non-tuberculous mycobacteria (NTM) are global concerns. The development of a rapid and accurate diagnostic method, capable of detecting and identifying different mycobacteria species, is crucial. We propose a molecular approach, the BiDz-TB/NTM, based on the use of binary deoxyribozyme (BiDz) sensors for the detection of Mycobacterium tuberculosis (Mtb) and NTM of clinical interest. A panel of DNA samples was used to evaluate Mtb-BiDz, Mycobacterium abscessus/Mycobacterium chelonae-BiDz, Mycobacterium avium-BiDz, Mycobacterium intracellulare/Mycobacterium chimaera-BiDz, and Mycobacterium kansasii-BiDz sensors in terms of specificity, sensitivity, accuracy, and limit of detection. The BiDz sensors were designed to hybridize specifically with the genetic signatures of the target species. To obtain the BiDz sensor targets, amplification of a fragment containing the hypervariable region 2 of the 16S rRNA was performed, under asymmetric PCR conditions using the reverse primer designed based on linear-after-the-exponential principles. The BiDz-TB/NTM was able to correctly identify 99.6% of the samples, with 100% sensitivity and 0.99 accuracy. The individual values of specificity, sensitivity, and accuracy, obtained for each BiDz sensor, satisfied the recommendations for new diagnostic methods, with sensitivity of 100%, specificity and accuracy ranging from 98% to 100% and from 0.98 to 1.0, respectively. The limit of detection of BiDz sensors ranged from 12 genome copies (Mtb-BiDz) to 2,110 genome copies (Mkan-BiDz). The BiDz-TB/NTM platform would be able to generate results rapidly, allowing the implementation of the appropriate therapeutic regimen and, consequently, the reduction of morbidity and mortality of patients.IMPORTANCEThis article describes the development and evaluation of a new molecular platform for accurate, sensitive, and specific detection and identification of Mycobacterium tuberculosis and other mycobacteria of clinical importance. Based on BiDz sensor technology, this assay prototype is amenable to implementation at the point of care. Our data demonstrate the feasibility of combining the species specificity of BiDz sensors with the sensitivity afforded by asymmetric PCR amplification of target sequences. Preclinical validation of this assay on a large panel of clinical samples supports the further development of this diagnostic tool for the molecular detection of pathogenic mycobacteria.