Search Results (59)

Mixed-type carcinoma (MTC) accounts for 44% of mammary neoplasms in bitches and poses challenges in histological grading due to the heterogeneity of invasive areas. The present study aimed to measure and characterize invasive areas in the stroma of MTC and investigate the association of those parameters with lymph node status and survival. Forty cases were analyzed and divided into two groups: with metastasis and without metastasis. The size, perimeter, length, and number of invasive carcinomatous areas were measured. Cases with metastasis showed a higher number of foci (p = 0.003) and larger invasive areas (p = 0.006) compared to cases without metastasis. Bitches with invasive areas larger than 2 mm² had shorter survival times. No association was found between the perimeter or length of invasive areas, the expression of Ki67, ER, PR, COX-2, HER-2, and the immunophenotype. Thus, the number and size of invasive areas are associated with regional lymph node status, suggesting histomorphometry may serve as a valuable tool for evaluating the biological behavior of mixed-type carcinoma. Full article

Background/Objectives: Data on the natural history and endoscopic treatment outcomes of recurrent anastomotic biliary stricture (RABS) after orthotopic liver transplantation (OLT) are limited. This study aimed to evaluate the incidence and outcomes of RABS after OLT. Methods: A retrospective single-center study on OLT patients who underwent successful endoscopic treatment of ABS was conducted. The incidence of RABS, risk factors for recurrence, and outcomes of repeat endoscopic therapy were recorded. Results: A total of 131 OLT patients with ABS underwent endoscopic treatment, of which 119 successfully completed an endoscopic treatment course. After a median follow-up of 51.5 months (IQR 18.5–86.25) from ABS resolution, 26/119 patients (22.7%) developed RABS. All patients with RABS underwent a second endoscopic treatment course; 24 patients received self-expandable metal stents and 2 received plastic stents. Re-treatment was successful in 21 patients (80.8%) after a median of 8.5 months (IQR 5.25–14.50) and a total of 62 ERCPs. Adverse events occurred in two patients (7.4%)—one bacteremia and one suprastenotic biliary stricture. After a median follow-up of 65.5 months (IQR 20.75–125.5) from stent removal, only one patient had a second recurrence, which was treated with a Roux-en-Y hepaticojejunostomy. Multivariate analysis showed that older age at ABS diagnosis (OR 1.1; 95% CI: 1.1–1.2 p = 0.04) was the only independent risk factor for recurrence. Conclusions: RABS affects more than 20% of patients after successful endoscopic treatment. A second endoscopic therapy with covered self-expandable metal stents is a safe and effective option and should be considered before more invasive options. Full article

Non-invasive prenatal testing (NIPT) has been widely adopted for the screening of chromosomal abnormalities; however, its adoption for monogenic disorders, such as β-thalassaemia, has proven challenging. Haemoglobinopathies are the most common monogenic disorders globally, with β-thalassaemia being particularly prevalent in Cyprus. This study introduces a non-invasive prenatal haplotyping (NIPH) assay for β-thalassaemia, utilizing cell-free DNA (cfDNA) from maternal plasma. The assay determines paternal inheritance by analyzing highly heterozygous single-nucleotide variants (SNVs) in the β-globin gene cluster. To identify highly heterozygous SNVs in the population, 96 randomly selected samples were processed using Illumina DNA-prep NGS chemistry. A custom, high-density NGS genotyping panel, named HAPLONID, was designed with 169 SNVs, including 15 common pathogenic ones. The AmpliSeq for Illumina assay was then applied to cfDNA to evaluate the panel’s efficiency in performing NIPT for β-thalassaemia. Analysis revealed 219 highly polymorphic SNVs, and the sequencing of 17 families confirmed successful paternal allele determination. The NIPH assay demonstrated 100% success in diagnostic interpretation. This study achieved the advancement of an integrated NGS-NIPT assay for β-thalassaemia, bringing it one step closer to being a diagnostic assay and thereby enabling a reduction in the number of risky invasive prenatal sampling procedures in Cyprus and elsewhere. Full article

The literature on the postprandial metabolic changes in individuals with Metabolic Syndrome (MetS) remains limited, despite the fact that postprandial states represent the most common physiological condition in Western societies. Background/Objectives: The objective of this study was to investigate the plasma metabolomics profile in both fasting and postprandial states following a high-fat challenge in individuals with MetS who consumed diets with varying quantities and qualities of dietary fat over 12 weeks. Methods: Seventy-five patients with MetS (28 males and 47 females) from the Spanish LIPGENE cohort were included in the study. MetS patients were randomly stratified to follow one of four dietary interventions (isoenergetic diets) for a 12-week long-term study. The four diets were high in saturated fatty acids and high in monounsaturated fatty acids (HSFA and HMUFA), low-fat high-complex carbohydrates (LFHCC), and LFHCC supplemented with n-3. The metabolomics analysis of plasma samples was carried out using Liquid Chromatography Time-of-Flight Mass Spectrometry (LC-TOF/MS). Results: We observed a decrease in inflammation biomarkers, including acetylcarnitine and L-carnitine during the fasting state and hexanoyl-L-carnitine and isobutyryl-L-carnitine during the postprandial period, mediated by the replacement of HSFA with HMUFA. Additionally, antioxidant compounds such as 4-hydroxybenzaldehyde and L-valine were expressed at higher levels after consumption of the HMUFA diet compared to the HSFA diet. HSFA also presented altered levels of phosphatidylcholine, a metabolite previously linked with insulin resistance. Conclusions: These findings suggest that replacing HSFA with HMUFA may reduce inflammation and improve antioxidant profiles, supporting the potential for tailored dietary interventions in individuals with MetS. Full article

Empowerment, the process by which a person is enabled to increase control over decisions concerning their life, is a multidimensional construct that has been extensively discussed by various disciplines for more than four decades. Several empowerment models have been presented, based on different approaches. This paper proposes a four-step model, based on individual and contextual awareness and advancement. Disparate factors may positively or negatively affect empowerment, including gender, race, culture, education, financial autonomy, socioeconomic status, family, neighborhood, religion, social cohesion, civic society, and political context. Empowerment has been extensively discussed in parallel with health promotion, since it is expected to positively affect health, both on the level of the individual and community, as well as in the context of the patient–healthcare professional relationship. Considering the position of women in patriarchal societies, where women may experience feelings of powerlessness, their social position and more importantly health may be adversely affected. Gender biases that were developed due to the marginalized position of women in different societies, coupled with paternalistic approaches of healthcare professionals, may significantly contribute to higher comorbidity, albeit longer life expectancy for women. Empowerment can therefore be a powerful tool for achieving equity in health and improving women’s well-being. Full article

The additive manufacturing technique performed via laser powder bed fusion has matured as a technology for manufacturing cemented carbide parts. The parts are built by additive consolidation of thin layers of a WC and Co mixture using a laser, depending on the power and scanning speed, making it possible to create small, complex parts with different geometries. NbC-based cermets, as the main phase, can replace WC-based cemented carbides for some applications. Issues related to the high costs and dependence on imports have made WC and Co powders emerge as critical raw materials. Furthermore, avoiding manufacturing workers’ health problems and occupational diseases is a positive advantage of replacing WC with NbC and alternative binder phases. This work used WC and NbC as the main carbides and three binders: 100% Ni, 100% Co, and 50Ni/50Co wt.%. For the flowability and spreadability of the powders of WC- and NbC-based alloy mixtures in the powder bed with high cohesiveness, it was necessary to build a vibrating container with a pneumatic turbine ranging from 460 to 520 Hz. Concurrently, compaction was promoted by a compacting system. The thin deposition layers of the mixtures were applied uniformly and were well distributed in the powder bed to minimize the defects and cracks during the direct sintering of the samples. The parameters of the L-PBF process varied, with laser scanning speeds from 25 to 125 mm.s^─1 and laser power from 50 to 125 W. Microstructural aspects and the properties obtained are presented and discussed, seeking to establish the relationships between the L-PBF process variables and compare them with the liquid phase sintering technique. Full article

Endemic and pandemic viruses represent significant public health challenges, leading to substantial morbidity and mortality over time. The COVID-19 pandemic has underscored the urgent need for the development and discovery of new, potent antiviral agents. In this study, we present the synthesis and anti-SARS-CoV-2 activity of a series of benzocarbazoledinones, assessed using cell-based screening assays. Our results indicate that four compounds (4a, 4b, 4d, and 4i) exhibit EC50 values below 4 μM without cytotoxic effects in Calu-3 cells. Mechanistic investigations focused on the inhibition of the SARS-CoV-2 main protease (Mpro) and papain-like protease (PLpro) have used enzymatic assays. Notably, compounds 4a and 4b showed Mpro inhibition activity with IC50 values of 0.11 ± 0.05 and 0.37 ± 0.05 µM, respectively. Furthermore, in silico molecular docking, physicochemical, and pharmacokinetic studies were conducted to validate the mechanism and assess bioavailability. Compound 4a was selected for preliminary drug-likeness analysis and in vivo pharmacokinetics investigations, which yielded promising results and corroborated the in vitro and in silico findings, reinforcing its potential as an anti-SARS-CoV-2 lead compound. Full article

No consensus exists on whether acute aerobic exercise alters the glomerular filtration rate in older adults. Objective: To assess the immediate effects of three aerobic exercise intensities on the estimated glomerular filtration rate (eGFR) in healthy, sedentary older adults. Methods: Eighteen healthy, sedentary older adults (ten men and eight women) voluntarily participated in this study. The participants underwent three standardized aerobic exercise tests (100%, 80%, and 60% of the maximal heart rate) on a bicycle ergometer. Blood samples were collected to determine cholesterol, triacylglycerols, glucose, serum creatinine (Cr), Cystatin C (CysC) concentrations, and eGFR. Results: eGFR and serum concentrations of Cr and CysC were not modified at any exercise intensity. There was a negative correlation between blood total cholesterol vs. eGFR (R = −0.512, R = −0.582, R = −0.531; p < 0.05) at rest, 60%, and 100% of the maximal heart rate, respectively. In addition, a negative correlation existed for age vs. eGFR at 60% of the maximal heart rate (R = −0.516; p < 0.05). Conclusions: Short-duration aerobic exercise of low, moderate, and vigorous intensity did not significantly affect eGFR and is considered safe for kidney function in healthy, sedentary older adults. However, regular monitoring of kidney function in older people engaged in moderate- and high-intensity exercise is advised. Full article

This quantitative research analyzes the entrepreneurial competencies of in-migrant women in the Children’s Village of the Lambayeque Region. With a sample of 79 women, 39 Peruvian and 40 Venezuelan, online surveys and observation forms were operated for 18 months (2021–2022). Using a Likert scale of 55 questions and nine dimensions, competencies such as opportunity seeking, risk anticipation, persistence, self-exertion, and more were assessed. Data were analyzed using correlations, ANOVA, logistic regression, and principal component analysis (PCA). The results revealed significant differences between nationalities, with Venezuelan women having higher competencies. The study identified two principal components that explain 57.663% of the total variance, representing initiative and quality, as well as control and responsibility. These findings suggest the need for specific training programs to strengthen the entrepreneurial competencies of these women. The inductive methodology and quantitative analysis provided a clear vision of entrepreneurial competencies, contributing to the improvement of support and training programs. Full article

Background: We investigate the role of galantamine on autonomic dysfunction associated with early cardiometabolic dysfunction in the offspring of fructose-overloaded rats. Methods: Wistar rats received fructose diluted in drinking water (10%) or water for 60 days prior to mating. Fructose overload was maintained until the end of lactation. The offspring (21 days after birth) of control and fructose-overloaded animals were divided into three groups: control (C), fructose (F) and fructose + galantamine (GAL). GAL (5 mg/kg) was administered orally until the offspring were 51 days old. Metabolic, hemodynamic and cardiovascular autonomic modulation were evaluated. Results: The F group showed decreased insulin tolerance (KITT) compared to the C and GAL groups. The F group, in comparison to the C group, had increased arterial blood pressure, heart rate and sympathovagal balance (LF/HF ratio) and a low-frequency band of systolic arterial pressure (LF-SAP). The GAL group, in comparison to the F group, showed increased vagally mediated RMSSD index, a high-frequency band (HF-PI) and decreased LF/HF ratio and variance in SAP (VAR-SAP) and LF-SAP. Correlations were found between HF-PI and KITT (r = 0.60), heart rate (r = −0.65) and MAP (r = −0.71). Conclusions: GAL treatment significantly improved cardiovascular autonomic modulation, which was associated with the amelioration of cardiometabolic dysfunction in offspring of parents exposed to chronic fructose consumption. Full article

Geochemical mapping is the base of knowledge needed to determine the critical contents of potential toxic elements and the potentially hazardous regions on the planet. This work presents maps of baseline values of chemical elements in the soils of Sal Island (Cape Verde) and the assessment of their ecological and human health risks. According to the results, Ba, Co, Ni, and V baseline values are above the international guidelines for agricultural and residential proposed uses. Arsenic in the soil overlying the Ancient Eruptive Complex shows a high potential ecological risk factor. It is not clear if high As contents in soils have a geogenic or anthropogenic source. Hazard indexes (HI) were calculated for children and adults. For children, HI is higher than 1 for Co, Cr, and Mn, indicating potential non-carcinogenic risk. These elements are present in high content in soils covering Quaternary sediments, the Monte Grande-Pedra Lume Formation, and the Ancient Eruptive Complex, inducing belief in a geogenic source. For the other elements and for adults, there is no potential non-carcinogenic risk. Cancer risk (CR) was calculated for As, Cd, Cr, and Ni exposures for adults and children, and the results are mainly lower than the carcinogenic target risk value, indicating no cancer risk. Only in a few soil samples are CR results slightly higher than the carcinogenic target risk of 1 × 10⁻⁴ 2 × 10⁻⁶ for adults exposed to Cr by inhalation. It is important to emphasize that these results of the health risk associated with exposure are likely to overestimate the bioavailable fractions of the elements in the soil once it is used as aqua regia instead of physiological fluids to digest the soil. However, since measured concentrations of potential toxic elements in soil reveal that they can be harmful to both the environment and human health, regional activities such as agriculture or water exploitation must be controlled by competent authorities. These conclusions highlight the insights and the applicability of soil geochemistry surveys for future policy progress, which are particularly relevant in developing countries like the Cape Verde archipelago. Full article

Hepatocellular carcinoma (HCC) development is associated with altered modifications in DNA methylation, changing transcriptional regulation. Emerging evidence indicates that DNA methyltransferase 1 (DNMT1) plays a key role in the carcinogenesis process. This study aimed to investigate how pirfenidone (PFD) modifies this pathway and the effect generated by the association between c-Myc expression and DNMT1 activation. Rats F344 were used for HCC development using 50 mg/kg of diethylnitrosamine (DEN) and 25 mg/kg of 2-Acetylaminofluorene (2-AAF). The HCC/PFD group received simultaneous doses of 300 mg/kg of PFD. All treatments lasted 12 weeks. On the other hand, HepG2 cells were used to evaluate the effects of PFD in restoring DNA methylation in the presence of the inhibitor 5-Aza. Histopathological, biochemical, immunohistochemical, and western blot analysis were carried out and our findings showed that PFD treatment reduced the amount and size of tumors along with decreased Glipican-3, β-catenin, and c-Myc expression in nuclear fractions. Also, this treatment improved lipid metabolism by modulating PPARγ and SREBP1 signaling. Interestingly, PFD augmented DNMT1 and DNMT3a protein expression, which restores global methylation, both in our in vivo and in vitro models. In conclusion, our results suggest that PFD could slow down HCC development by controlling DNA methylation. Full article

Background: This study investigated effects of rapid high-intensity light-curing (3 s) on increasing transdentinal temperature and cell viability. Methods: A total of 40 dentin discs (0.5 mm) obtained from human molars were prepared, included in artificial pulp chambers (4.5 × 5 mm), and subjected to four light-curing protocols (n = 5), with a Valo Grand light curing unit: (i) 10 s protocol with a moderate intensity of 1000 mW/cm² (Valo-10 s); (ii) 3 s protocol with a high intensity of 3200 mW/cm² (Valo-3 s); (iii) adhesive system + Filtek Bulk-Fill Flow bulk-fill composite resin in 10 s (FBF-10 s); (iv) adhesive system + Tetric PowerFlow bulk-fill composite resin in 3 s (TPF-3 s). Transdentinal temperature changes were recorded with a type K thermocouple. Cell viability was assessed using the MTT assay. Data were analyzed using one-way ANOVA and Tukey tests for comparison between experimental groups (p < 0.05). Results: The 3 s high-intensity light-curing protocol generated a higher temperature than the 10 s moderate-intensity standard (p < 0.001). The Valo-10 s and Valo-3 s groups demonstrated greater cell viability than the FBF-10s and TPF-3 s groups and statistical differences were observed between the Valo-3 s and FBF-10 s groups (p = 0.023) and Valo-3 s and TPF-3 s (p = 0.025), with a potential cytotoxic effect for the FBF-10 s and TPF-3 s groups. Conclusions: The 3 s rapid high-intensity light-curing protocol of bulk-fill composite resins caused a temperature increase greater than 10 s and showed cell viability similar to and comparable to the standard protocol. Full article

Recent studies have found increased cardiovascular mortality risk in patients with type 1 diabetes when compared to normoglycemic people, even when they were kept under good glycemic control. However, the mechanisms underlying this condition have yet to be fully understood. Using streptozotocin (STZ)-induced diabetic rats, we evaluated the effects of insulin replacement therapy on cardiac, autonomic, inflammatory, and oxidative stress parameters. Daily treatment with insulin administrated subcutaneously in the STZ-diabetic rats showed a reduction in hyperglycemia (>250 mg/dL) to normalized values. The insulin treatment was effective in preventing alterations in cardiac morphometry and systolic function but had no impact on diastolic function. Also, the treatment was not able to prevent the impairment of baroreflex-tachycardic response and systolic arterial pressure variability (SAP-V). A correlation was found between improvement of these autonomic parameters and higher levels of IL-10 and lower levels of oxidized glutathione. Our findings show that insulin treatment was not able to prevent diastolic, baroreflex, and SAP-V dysfunction, suggesting an outstanding cardiovascular risk, even after obtaining a good glycemic control in STZ-induced diabetic rats. This study shed light on a relatively large population of diabetic patients in need of other therapies to be used in combination with insulin treatment and thus more effectively manage cardiovascular risk. Full article

The +33 C>G variant [NM_000518.5(HBB):c.-18C>G] in the 5′ untranslated region (UTR) of the β-globin gene is described in the literature as both mild and silent, while it causes a phenotype of thalassemia intermedia in the presence of a severe β-thalassemia allele. Despite its potential clinical significance, the determination of its pathogenicity according to established standards requires a greater number of published cases and co-segregation evidence than what is currently available. The present study provides an extensive phenotypic characterization of +33 C>G using 26 heterozygous and 11 compound heterozygous novel cases detected in Cyprus and employs computational predictors (CADD, RegulomeDB) to better understand its impact on clinical severity. Genotype identification of globin gene variants, including α- and δ-thalassemia determinants, and rs7482144 (XmnI) was carried out using Sanger sequencing, gap-PCR, and restriction enzyme digestion methods. The heterozygous state of +33 C>G had a silent phenotype without apparent microcytosis or hypochromia, while compound heterozygosity with a β+ or β0 allele had a spectrum of clinical phenotypes. Awareness of the +33 C>G is required across Mediterranean populations where β-thalassemia is frequent, particularly in Cyprus, with significant relevance in population screening and fetal diagnostic applications. Full article