Search Results (20,209)

Equal access to health initiatives and services under the principles of universal and comprehensive care remains a challenge in Brazil. The realization of public health policies is further intricate when one examines the health situation of people deprived of liberty. This study showcases the “Prison System: Beyond the Walls” educational pathway, available on the Virtual Learning Environment of the Brazilian National Health System (AVASUS). The action research methodological strategy guided the pathway development, emphasizing dialogic learning. The goal was to address the need for massive training on the topic of prison health, with the model focusing on engagement through spontaneous, non-mandatory participation in the pathway courses. The pathway comprised four modules, whose educational offerings were based on the self-learning model. Students were free to choose which courses to take and in what order, as there was no prerequisite for participating in modules. Hence, students could either take all the courses or only those with which they identify their learning needs, regardless of work demands or personal interests. Structuring the pathway through action research facilitated a massive, cohesive, and continuous training process. This approach expanded knowledge and established meaningful relationships among the related topics and the key players involved: health professionals, prison officers, and people deprived of liberty. Notably, the pathway courses have surpassed the 50,000-enrollment mark, spanning all five regions of Brazil. In this context, this article presents and discusses the development of the “Prison System: Beyond the Walls” pathway, emphasizing the massive improvement of health within Brazil’s prison system and highlighting the results achieved. Full article

Intrahepatic cholangiocarcinoma (ICC) is a highly heterogeneous malignancy. The reasons behind the global rise in the incidence of ICC remain unclear, and there exists limited knowledge regarding the immune cells within the tumor microenvironment (TME). In this study, a more comprehensive analysis of multi-omics data was performed using machine learning methods. The study found that the immunoactivity of B cells, macrophages, and T cells in the infiltrating immune cells of ICC exhibits a significantly higher level of immunoactivity in comparison to other immune cells. During the immune sensing and response, the effect of antigen-presenting cells (APCs) such as B cells and macrophages on activating NK cells was weakened, while the effect of activating T cells became stronger. Simultaneously, four distinct subpopulations, namely ${\mathrm{B}}^{\mathrm{L}\mathrm{p}}$, ${\mathrm{M}\mathrm{a}\mathrm{c}\mathrm{r}\mathrm{o}\mathrm{p}\mathrm{h}\mathrm{a}\mathrm{g}\mathrm{e}\mathrm{s}}^{\mathrm{L}\mathrm{p}}$, ${\mathrm{B}}^{\mathrm{H}\mathrm{n}}$, and ${\mathrm{T}}^{\mathrm{H}\mathrm{n}}$, have been identified from the infiltrating immune cells, and their corresponding immune-related marker genes have been identified. The immune sensing and response model of ICC has been revised and constructed based on our current comprehension. This study not only helps to deepen the understanding the heterogeneity of infiltrating immune cells in ICC, but also may provide valuable insights into the diagnosis, evaluation, treatment, and prognosis of ICC. Full article

Background/Objectives: The relationship between pathologic findings in soft tissue sarcoma (STS) after neoadjuvant treatment and oncological outcomes remains uncertain due to varying evaluation methods and cut-off values. This study aims to assess pathologic findings after neoadjuvant radiotherapy in STS using the EORTC-STBSG response score and evaluate its prognostic value. Methods: Clinical and outcome data from 44 patients were reviewed. Resected specimens were re-evaluated to measure viable cells, necrosis, fibrosis, and hyalinization. Local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were analyzed using Kaplan–Meier survival analysis. Cox proportional hazards regression was used for univariate and multivariate analyses to correlate outcomes with pathologic response. Results: The median percentages of viable cells, necrosis, and fibrosis/hyalinization were 20%, 11%, and 40%, respectively. A pathologic complete response (pCR), defined as ≤5% viable cells, was achieved in 25% of cases. Local recurrence occurred in 33% of cases, with a significantly higher rate of 64% after R1 resection compared to 22% after R0 resection. Distant metastases were observed in 42% of patients, primarily in the lungs. The 3-year rates for LRFS, DMFS, and OS were 65%, 54%, and 67%, respectively. A correlation between outcomes and tumor size, grade and histological subtype was observed. Classifying pathologic response by the EORTC-STBSG score failed to show an association with outcomes. Patients achieving pCR showed lower risk of LR and improved OS. Conclusions: While the EORTC-STBSG score did not show a prognostic value, resection specimens with ≤5% viable cells were linked to improved LRFS and OS. Full article

Gastrin is an important hormone involved in gastric acid secretion. Despite its importance, validated methods other than radioimmunoassay (RIA) to assess serum gastrin concentrations in horses are lacking. This study aims to determine the agreement between ELISA and RIA in quantifying equine serum gastrin concentrations. Serum gastrin concentrations were quantified using two ELISA kits and RIA. Samples (196) from 14 horses at different time points were analyzed using one ELISA kit and RIA, selected samples (7) were analyzed using a second ELISA kit, and the correlation between methods was calculated. The level of agreement was analyzed by Bland-Altman analysis and differences between ELISA and RIA were plotted against averages for each sample. The Pearson correlation between gastrin concentrations measured by ELISA and the RIA was 0.27 and −0.32 for ELISA kit 1 and kit 2, respectively. Mean bias (ELISA-RIA) was 198.40 pg/mL (95% CI: −142.95–539.76) and −17.90 pg/mL (95% CI: −89.98–54.19) for ELISA kit 1 and kit 2, respectively. Measurements of horse gastrin by both ELISA methods were highly variable, with an unacceptable correlation to the reference method, RIA. Using non-validated ELISA methods to quantify horse gastrin cannot be recommended. Full article

Reniform nematode (Rotylenchulus reniformis) causes significant yield loss in cotton worldwide. In 2012, its detection in the Dawson-Callide region of Central Queensland prompted extensive surveys of cotton fields. The nematode was confirmed in 68% of sampled fields, with populations ranging from 2 to 3870 R. reniformis/200 mL of soil. Soil monitoring revealed increasing populations associated with consecutive cotton crops. However, when corn or sorghum replaced cotton, soil nematode populations significantly decreased. A two-year replicated field trial demonstrated that growing a non-host crop (such as biofumigant sorghum ‘Fumig8tor’, grain sorghum, or corn) significantly reduced nematode populations in the top 15 cm of soil compared to cotton. Unfortunately, when cotton was replanted the following season, nematode populations rebounded regardless of the previous crop. Only the ‘Fumig8tor’-cotton rotation resulted in significantly lower nematode populations than continuous cotton. Vertical soil sampling showed that rotating with a non-host crop significantly reduced nematode densities to a depth of 100 cm compared to cotton. However, when the field was replanted with cotton, nematode populations recovered, unaffected by cropping or soil depth. This study emphasises the importance of monitoring reniform nematodes in cotton soils for early detection and defining distribution patterns within a field, which may improve the effectiveness of management practices. These results suggest that one rotation out of cotton is not sufficient, as populations return to high levels when cotton is grown again. Therefore, two or more rotations out of cotton should be considered to manage this nematode. Full article

Background/Objectives: Rivaroxaban and dabigatran are commonly used for thromboembolic disease management in active cancer patients. However, limited research explores the impact of concurrent chemotherapy on the pharmacodynamics of direct oral anticoagulants (DOAC). The aim of our study was to evaluate the impact of combined chemotherapy with rivaroxaban and dabigatran on the pharmacodynamics in patients with diffuse large B-cell lymphoma (DLBCL).; Methods: This was a prospective, pharmacodynamic study. Eligible subjects were ≥18 years old, diagnosed with DLBCL and initiating R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) immunochemotherapy. The enrolled adults received either rivaroxaban (10 mg once daily) or dabigatran etixalate (110 mg twice daily). Plasma anti-factor Xa (FXa) in participants on rivaroxaban and diluted thrombin time (dTT) in participants on dabigatran were assessed over the dosing interval before and after R-CHOP administration. Pharmacodynamic parameters of rivaroxaban and dabigatran were determined using a non-compartmental analysis.; Results: Twenty-six adults participated, with twelve in the rivaroxaban group and fourteen in the dabigatran group. The mean age was 59 ± 14.4 years. In the rivaroxaban group, the AUEC of FXa inhibition showed no significant change after R-CHOP (mean difference 3.8 ng·h/mL, 95% confidence interval (CI) −155.4 to 163.0, p = 0.96). Similarly, in the dabigatran group, the AUEC of dTT remained unchanged post R-CHOP (mean difference 54.41 ng·h/mL, 95% CI −99.09 to 207.9 ng/mL, p = 0.46). However, the median time-to-peak dTT was significantly faster with R-CHOP (3 h, [min–max, 1.5–8] compared to without it (4 h, [min–max, 3–8], p = 0.04); Conclusions: Concurrent R-CHOP chemotherapy did not significantly impact FXa inhibition by rivaroxaban or dTT by dabigatran. The time-to-peak dTT was faster when dabigatran was administered with R-CHOP. Full article

Background: Existing bioanalytical methods for verapamil hydrochloride (VH) are often complex, requiring advanced instrumentation and specialized expertise, which limits their use in resource-constrained laboratories. Aim: The goal of this study is to fill this gap by developing a simplified, robust RP-HPLC-UV approach for the estimation of verapamil hydrochloride in rabbit plasma. Designed to enhance accuracy and precision while minimizing sample preparation challenges, this method addresses existing limitations by providing an affordable and reliable alternative for laboratories lacking sophisticated instrumentation. Methods: The bioanalytical method was implemented on C-18 stationary phase (5 μ, 250 × 4.6 mm) using acetonitrile/0.1% tetrahydrofuran (THF) in water (80:20, in volume) as the liquid system at a 1 mL/min flow speed, employing carvedilol as an internal standard. Results: The reported retention times of verapamil hydrochloride and carvedilol were ~7.64 and 4.69 min, respectively, at sufficiently high system suitability standards. The linearity of the bioanalytical approach can be seen between 0.025 and 5.0 µg/mL (r² = 0.9991). The findings indicated that there was no matrix influence in terms of accuracy (≥98.96 ± 2.68%), intra- and inter-day precision (≤3.68%), recovery (101.98 ± 2.76%), and procedure efficiency (100.65 ± 1.82%). Benchtop, long-term, and short-term stability investigations all revealed that the verapamil hydrochloride in the bio-samples was stable. The pharmacokinetic parameters (Cmax—3.47 µg/mL; Tmax—1.59 h) were studied from time-dependent plasma concentrations of verapamil hydrochloride estimated after 40 mg oral dosing in New Zealand white rabbits. Conclusions: The developed bioanalytical method provided easier quantitative analysis of verapamil hydrochloride from rabbit plasma and was effectively used in a pharmacokinetic investigation of an oral bolus. The reliable performance of this method under practical conditions positions it as a crucial tool for advancing pharmacokinetic studies across various research environments. Full article

With the widespread use of integrase inhibitors and the expanding use of long-acting cabotegravir in both pre-exposure prophylaxis and antiretroviral treatment, molecular surveillance on the transmission of integrase resistance has regained clinical significance. This study aimed to determine the frequency of INSTI-transmitted drug resistance mutations (DRMs) among treatment-naïve individuals in Poland from 2016 to 2023. INSTI resistance was analyzed in 882 antiretroviral treatment-naïve individuals using Sanger sequencing. Integrase DRMs were defined based on the Stanford HIV drug resistance database scores. Phylogeny was used to investigate subtyping and clustering. For the analysis of time-trends, logistic regression was used. Major (E138K and R263K) integrase mutations were detected in 0.45% of cases with minor resistance observed in 14.85%, most commonly (13.95%) E157Q. Overall, no major clusters of transmitted drug resistance were identified, and the transmission of E157Q showed a decreasing trend (p < 0.001). While the frequency of sub-subtype A6 increased, it was predominantly found among migrants and associated with L74 mutations. The frequency of major integrase-transmitted DRMs remains low, despite the changes in subtype variability. Surveillance of changing HIV molecular variation patterns is vital from the perspective of the optimal use of integrase inhibitors, especially due to expanding long-acting cabotegravir implementation. Full article

(1) Background: The genus Phyllostachys belongs to the subfamily Bambusoideae within the family Gramineae. Bamboos of this genus are distinguished by their remarkable genetic traits, including exceptional resistance to both cold and drought conditions. These species possess considerable economic, ecological, and aesthetic value, finding extensive use in forestry and landscape design across China. (2) Methods: This study employed Illumina’s second-generation sequencing technology to sequence the chloroplast genomes of eight Phyllostachys species, followed by their assembly and annotation. (3) Results: The chloroplast genomes of the genus exhibit a characteristic tetrad structure with an average sequence length of 139,699 bp and an average GC content of 38.9%. A total of 130 genes have been annotated across eight bamboo species, comprising 75 protein-coding genes, 28 tRNA genes, and four rRNA genes. Global alignment and nucleotide polymorphism analyses indicate that the chloroplast genome of Phyllostachys is highly conserved overall. The boundaries of the four chloroplast regions are relatively conserved and exhibit minimal differences. Among these regions, three coding region genes—atpH, trnQ-UUG, and petB—and five non-coding regions—rpl32-trnL-UAG, rpl14-rpl16, rpl22-rps19, rps12-clpP, and trnR-UCU-trnM-CAU—exhibit high polymorphism and can be used as potential hotspot areas for subsequent research. A total of 266 simple sequence repeat (SSR) loci were identified by SSR analysis in the chloroplast genomes of eight bamboo species; the largest number of mononucleotide repeats was 154, predominantly consisting of A/T. Codon bias in the chloroplast genomes of the eight bamboo species indicates a preference for codons ending with A and U. Additionally, the UUA codon, which encodes leucine (Leu), is positioned between codons encoding phenylalanine (Phe), lysine (Lys), leucine (Leu), serine (Ser), and tyrosine (Tyr), indicating certain differences among these species. (4) Conclusions: This study aims to offer novel insights into the population genetics, phylogenetic relationships, and evolutionary patterns of Phyllostachys. Full article

The global prevalence of cardiovascular diseases (CVDs), including dyslipidemia and atherosclerosis, is rising. While pharmacological treatments for dyslipidemia and associated CVDs exist, not all individuals can afford them, and those who do often experience adverse side effects. Preclinical studies have indicated the potential benefits of Abelmoschus esculentus and its active phytochemicals in addressing dyslipidemia in rodent models of diabetes. However, there is limited clinical evidence on lipid parameters. Thus, this study aimed to assess the potential impact of Abelmoschus esculentus on dyslipidemia. A literature search was performed on PubMed, Scopus, and Cochrane Library for relevant trials published from inception until 11 August 2024. Data analysis was performed using Jamovi software version 2.4.8 and Review Manager (version 5.4), with effect estimates reported as standardized mean differences (SMDs) and 95% confidence intervals (CI). The evidence from eight studies with nine treatment arms showed that Abelmoschus esculentus reduces total cholesterol (TC), SMD = −0.53 (95% CI: −1.00 to −0.07), p = 0.025), compared to placebo. Additionally, triglyceride (TG) was reduced in Abelmoschus esculentus compared to placebo, SMD = −0.24 (95% CI: −0.46 to −0.02), p = 0.035. Furthermore, low-density lipoprotein (LDL) was also reduced, SMD = −0.35 (95% CI: −0.59 to −0.11), p = 0.004 in Abelmoschus esculentus versus placebo. This remedy substantially increased high-density lipoprotein (HDL), SMD = 0.34 (95% CI: 0.07 to 0.61), p = 0.014). Abelmoschus esculentus substantially improved lipid profile in prediabetes, T2D, obesity, and diabetic nephropathy. While the evidence confirms the potential benefits of Abelmoschus esculentus in reducing dyslipidemia, it is important for future clinical studies to standardize the effective dosage for more reliable results. Therefore, future trials should focus on these markers in well-designed trials with sufficient sample sizes. Furthermore, Abelmoschus esculentus can be supplemented to the diet of the relevant populations to alleviate dyslipidemia. Full article

In October 2023, a disease outbreak in pufferfish (Takifugu obscurus) farms in Zhongshan City, Guangdong, China, caused high mortality. Diseased fish (mean length: 15 ± 1 cm) exhibited swimming disorders, fin rot, hemorrhage, and an enlarged spleen. Histopathological observations generally revealed inflammation, necrosis, and congestion in the spleen, kidneys, and brain tissues. The most severe pathological changes included interstitial edema and tubular atrophy in the kidneys, hemosiderin deposition in the spleen, massive red blood cell infiltration, and a decrease in lymphocytes. A single strain of bacteria (Tol-1) was isolated from the diseased pufferfish and identified as a Gram-positive streptococcus strain, exhibiting α-hemolysis on sheep blood agar plates. Through biochemical characterization, 16S rDNA sequencing, morphological analysis, and specific primer-based identification, the Tol-1 strain was identified as Lactococcus garvieae, serotype I. Antimicrobial susceptibility testing indicated that Tol-1 was sensitive to Chloramphenicol, Ampicillin, Cephalexin, and Doxycycline, but resistant to Kanamycin, Gentamicin and Ciprofloxacin. In addition, 15 common virulence factors were detected in the Tol-1 strain, including adhPav, adhPsaA, adhC I–II, adh, and hly 1–3. Pufferfish (mean length: 17 ± 1 cm) subjected to artificial infection via intraperitoneal injection (IP) with the Tol-1 strain exhibited clinical symptoms and histopathological damage similar to those observed in naturally infected fish. An infection dose of 1 × 10⁵ CFU/fish resulted in 80% mortality. The study fulfilled Koch’s postulates, indicating that the disease outbreak in pufferfish was caused by L. garvieae, which exhibited a high mortality rate in pufferfish despite the subtle clinical symptoms. These results serve as a warning for pufferfish farming areas and provide a scientific basis for future prevention and control efforts. Full article

Despite the recent development of improved methods of treating melanoma such as targeted therapy, immunotherapy or combined treatment, the number of new cases worldwide is increasing. It is well known that active metabolites of vitamin D₃ and lumisterol (L₃) exert photoprotective and antiproliferative effects on the skin, while UV radiation is a major environmental risk factor for melanoma. Thus, many natural metabolites and synthetic analogs of steroidal and secosteroidal molecules have been tested on various cancer cells and in animal models. In this study, we tested the anti-melanoma properties of several natural derivatives of vitamin D₃ and L₃ in comparison to 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃). A significant decrease in melanoma cell proliferation and cell mobility was observed for selected derivatives, with (25R)-27-hydroxyL₃ showing the highest potency (lowest IC50) in A375 cells but lower potency in SK-MEL-28 cells, whereas the parent L₃ failed to inhibit proliferation. The efficacy (% inhibition) by 1,24,25(OH)₃D₃ and 1,25(OH)₂D₃ were similar in both cell types. 1,25(OH)₂D₃ showed higher potency than 1,24,25(OH)₃D₃ in SK-MEL-28 cells, but lower potency in A375 cells for the inhibition of proliferation. As for 1,25(OH)₂D₃, but not the other derivatives tested, treatment of melanoma cells with 1,24,25(OH)₃D₃ markedly increased the expression of CYP24A1, enhanced translocation of the vitamin D receptor (VDR) from the cytoplasm to the nucleus and also decreased the expression of the proliferation marker Ki67. The effects of the other compounds tested were weaker and occurred only under certain conditions. Our data indicate that 1,24,25(OH)₃D₃, which has undergone the first step in 1,25(OH)₂D₃ inactivation by being hydroxylated at C24, still shows anti-melanoma properties, displaying higher potency than 1,25(OH)₂D₃ in SK-MEL-28 cells. Furthermore, hydroxylation increases the potency of some of the lumisterol hydroxy-derivatives, as in contrast to L₃, (25R)-27(OH)L₃ effectively inhibits proliferation and migration of the human malignant melanoma cell line A375. Full article

Background: Eosinophilic oesophagitis (EoE) is an immune-mediated oesophageal disorder causing dysphagia. Patients with EoE experience reduced QoL due to symptoms; however, this has not been assessed in the New Zealand population. The aim of this study was to assess QoL in patients with EoE in New Zealand. Methods: This observational study recruited participants from two New Zealand hospitals. Records were reviewed to confirm diagnoses, and consenting participants completed an electronic survey, consisting of the Dysphagia Symptom Questionnaire (DSQ) score and the QoL-specific EoE (EoE-QoL-A) questionnaire score. Correlation analysis examined the relationship between the DSQ and EoE-QoL-A scores. Differences in baseline variables were assessed. Univariate logistic regression assessed the association of variables with disease activity and QoL. Results: Fifty-four participants responded, and four were excluded due to incomplete surveys. The majority (76%) were male, and the median age was 47 years (IQR 42–58). The median DSQ was 49 (IQR 0–60), and the median EoE-QoL-A score was 68 (IQR 48–80). A reduced EoE-QoL-A score was associated with active disease (OR = 0.96,95% CI 0.926–0.995). Significant associations were found between disease activity and overall EoE-QoL-A score (r = −0.37, p < 0.01) as well as the sub-categories eating and diet (r = −0.54, p < 0.001), social (r = 0.30, p < 0.05), and emotional impact (r = −0.44, p < 0.01). The EOE-QoL-A score was higher in those on PPI (75 vs. 60, p = 0.02). Conclusion: This study identified a decreased quality of life (QoL) in individuals with EoE in New Zealand, aligning with international literature. The increased DSQ scores suggest a possible gap in current management approaches. The correlation between the DSQ and QoL highlights the need for improved care models of care for EoE. Full article

Based on our karyological findings in the Anacamptis Rich., Ophrys L., and Serapias L. genera, we have identified chromosomal markers within some hybrids and elucidated their interrelationships. Mitotic chromosomes of fifteen taxa were analyzed using the conventional Feulgen staining method. Only for Anacamptis ×gennarii (Rchb. f.) H.Kretzschmar, Eccarius & Dietr. [A. morio (L.) R.M.Bateman, Pridgeon & M.W.Chase × A. papilionacea (L.) R.M.Bateman, Pridgeon & M.W.Chase] and its parental species were some data obtained and reported with the banding method with Giemsa, Hoechst 33258 fluorochrome, and the FISH techniques. Our research involved new chromosomal measurements of fifteen taxa, including six hybrids, along with schematic representations. Morphometric parameters, i.e., M_CA and CV_CL, were used to evaluate karyotype asymmetry. Of meaning were the analyses performed on chromosomal complements of selected hybrids, which distinctly revealed marker chromosomes present in one or both putative parental species. Among the parents identified in some hybrids, Ophrys tenthredinifera Willd. has shown some interest due to the presence in its karyotype of a pair of chromosomes (n.1) showing a notable secondary constriction on the long arm. Indeed, one of the homologs is clearly distinguishable in the analyzed hybrids, where it clearly emerges as one of the putative parents. Given the challenges in detecting certain karyomorphological features within the Orchidinae subtribe using alternative methods, such as Giemsa C-banding or fluorescence banding, the Feulgen method remains valuable for cytogenetic characterization. It helps us to understand the genomes of hybrids and parental species, thus contributing to a deeper understanding of their genetic composition. Full article

Background. The left and right temporoparietal junctions (TPJs) are two brain areas involved in several brain networks, largely studied for their diverse roles, from attentional orientation to theory of mind and, recently, predictive processing. In predictive processing, one crucial concept is prior precision, that is, the reliability of the predictions of incoming stimuli. This has been linked with modulations of alpha power as measured with electrophysiological techniques, but TPJs have seldom been studied in this framework. Methods. The present article investigates, using magnetoencephalography, whether spontaneous oscillations in pre-stimulus alpha power in the left and right TPJs can modulate brain responses during a linguistic task that requires predictive processing in literal and non-literal sentences. Results. Overall, results show that pre-stimulus alpha power in the rTPJ was associated with post-stimulus responses only in the left superior temporal gyrus, while lTPJ pre-stimulus alpha power was associated with post-stimulus activity in Broca’s area, left middle temporal gyrus, and left superior temporal gyrus. Conclusions. We conclude that both the right and left TPJs have a role in linguistic prediction, involving a network of core language regions, with differences across brain areas and linguistic conditions that can be parsimoniously explained in the context of predictive processing. Full article