Ontogenetic and sexual differences in the venom of Bothrops moojeni: insights from a litter and its mother.

Variability in snake venom composition is well-documented and crucial for understanding snake ecology and predicting snakebites. In this study, we characterize the venom composition and biological activities of newborn female and male Bothrops moojeni and their mother. Our results reveal significant differences between the venom of newborn females and males, demonstrating a broad and diverse range of proteins. The venoms of newborn females showed higher serine protease effects, increased hemorrhagic activity, and greater lethality compared to the venom of newborn males. However, no differences were observed in phospholipase A2 and coagulant activity. The differences in protein composition and toxic activities between maternal and neonatal venom, as well as between the venoms of newborn females and males, contribute to understanding the diverse outcomes of snakebites. These results underscore the importance of considering sex and ontogeny in understanding venom composition in snakes.

Probiotics enhance alveolar bone microarchitecture, intestinal morphology and estradiol levels in osteoporotic animals.

BACKGROUND AND OBJECTIVE: Osteoporosis is associated with bone microarchitecture alterations, and the depletion of estrogen during menopause is a major contributing factor to its development. The literature highlights the noteworthy role of gut microbiota in bone metabolism, particularly in the progression of osteoporosis. Periodontal disease leads to alveolar bone loss, which may be influenced by estrogen deficiency, and this mechanism is intricately associated with an imbalance in systemic microbiota. The aim of this study was to evaluate the effects of Bifidobacterium animalis subsp. lactis HN019 (B. lactis HN019) and Lacticaseibacillus casei 01 (L. casei 01) administrations on an osteoporosis animal model. MATERIALS AND METHODS: Thirty-three female rats were randomly divided into three groups: control (C-OVX), C-OVX-HN019 and C-OVX-LC01. All animals were ovariectomized. In groups C-OVX-HN019 and C-OVX-LC01, the probiotics were administered for 4 months. All animals were euthanized after 16 weeks from ovariectomy. Microtomographic, histopathological and immunohistochemical examinations were conducted on periodontal tissues, whereas histomorphometry, histopathological and immunohistochemical analyses were carried out on the intestine. The levels of estradiol were assessed in blood using an immunoenzymatic assay. The data were subjected to statistical analyses (p < .05). RESULTS: The C-OVX-LC01 group exhibited a significant reduction in alveolar bone porosity and an increase in connective tissue density compared to C-OVX (p < .05). The C-OVX-HN019 and C-OVX-LC01 groups presented reduced expression of TRAP and RANKL compared to the C-OVX (p < .05). The C-OVX group presented villi defects, mild neutrophil infiltration, decrease in both villous height and intestinal crypts and reduced expression of intestinal junctional epithelium markers e-cadherin and claudin 01 compared to C-OVX-HN019 and C-OVX-LC01 (p < .05). The C-OVX group had lower estradiol levels than C-OVX-HN019 and C-OVX-LC01 (p < .05). CONCLUSION: The probiotic therapy promoted a reduction in alveolar bone destruction and intestinal permeability as well as an increase in estradiol levels in ovariectomized rats. Specifically, the probiotic strain Lacticaseibacillus casei 01 exhibited greater effectiveness compared to Bifidobacterium animalis subsp. lactis HN019, indicating strain-dependent outcomes.

When residents die in Portuguese care facilities: The experiences and practices of care facility directors before and during the COVID-19 pandemic.

This qualitative exploratory study aimed to describe the experiences and practices of care facility directors regarding residents dying in Portuguese residential care facilities (RCFs) before and during the COVID-19 pandemic. Data was obtained from 17 care director facilities who participated in focus groups. The data analysis followed the interpretative phenomenological approach. Participants stated that practices surrounding the death of the residents in Portuguese RCFs changed significantly from before to during the pandemic, regarding both those who died from COVID-19 infection and from other conditions. Four themes emerged that illustrated the situation during the peaks of the pandemic. During the pandemic, practices and experiences quite different from the usual ones have emerged. These results support the importance of a good death, and dying with dignity in RCFs, and the need for policies, practices, and training on the death of residents in RCFs in Portugal.

Mandibular Dysmorphology and Clinical Presentation in Treacher Collins Syndrome.

INTRODUCTION: Treacher Collins syndrome is a rare congenital disease characterized by the multiple craniofacial malformations. Although the deformities affecting patients with Treacher Collins syndrome have been well characterized, the effects of these malformations to clinical severity of the syndrome are not well understood. OBJECTIVE: To determine the association of specific Treacher Collins mandibular malformations with clinical severity. DESIGN: A retrospective radiographic observational study. SETTING: Study conducted at a single institution, a quaternary craniofacial care center. PATIENTS: 54 patients with Treacher Collins syndrome. INTERVENTIONS: Computed tomography (CT), clinical photographs and medical history were included in this analysis. Mandibles were isolated from CT data and reconstructed in three dimensions using Mimics software. Cephalometric measurements were performed on CT data. Clinical severity was determined by Teber and Vincent scores. Association of craniofacial dysmorphology to clinical severity was determined by Spearman rank coefficient. MAIN OUTCOME MEASURES: The main results obtained were the measurements of the mandibles and the quantification of the malformations of the evaluated patients. RESULTS: Among the most frequent findings in the sample are hypoplasia of the zygomatic complex, descending palpebral cleft and mandibular hypoplasia. Patients with a lower ramus/corpus ratio had a higher (more severe) Teber and Vincent classification. CONCLUSION: Patients with the most compromised mandible are also the patients with the highest number of malformations, thus, the most severe patients.

Does silicon attenuate PEG 6000-induced water deficit in germination and growth initial the seedlings corn.

Water stress limits the initial growth and development of maize mass and grain, as well as the physiological process for absorbing the amount of mineral elements. The objective was to evaluate the effect of silicon on germination and growth of corn seedlings submitted to water deficit. The experiment was carried out in the laboratory and the experimental design was completely randomized (factorial 3 × 4), with three concentrations of calcium silicate (0.0; 1.0 and 2.0 mM) and 4 solutions of PEG-6000 to simulate different osmotic potentials (0, 0; -0.3; -0.6; -0.9 MPa). Germination percentage, germination speed index (GSI), mean germination time (MGT), percentage of non-germinated and abnormal germinated, length and dry matter of shoot, root and total seedlings were evaluated. Water deficiency reduced the parameters TG, GSI and MGT. The water deficit reduce the MSPA, MSR and MST with more than 80% reduction in mass from seedlings without deficiency to seedlings with deficiency. For CPA, CR and CT there was a reduction of at least 87%, 70% and 77%, respectively, among seeds without deficiency compared to seeds submitted to deficiency. The use of silicon in corn seeds did not attenuate the stress caused by water deficit simulated by PEG-6000.

Accuracy and economic evaluation of screening tests for undiagnosed COPD among hypertensive individuals in Brazil.

In Brazil, prevalence of diagnosed COPD among adults aged 40 years and over is 16% although over 70% of cases remain undiagnosed. Hypertension is common and well-recorded in primary care, and frequently co-exists with COPD because of common causes such as tobacco smoking, therefore we conducted a cross-sectional screening test accuracy study in nine Basic Health Units in Brazil, among hypertensive patients aged ≥40 years to identify the optimum screening test/combinations to detect undiagnosed COPD. We compared six index tests (four screening questionnaires, microspirometer and peak flow) against the reference test defined as those below the lower limit of normal (LLN-GLI) on quality diagnostic spirometry, with confirmed COPD at clinical review. Of 1162 participants, 6.8% (n = 79) had clinically confirmed COPD. Peak flow had a higher specificity but lower sensitivity than microspirometry (sensitivity 44.3% [95% CI 33.1, 55.9], specificity 95.5% [95% CI 94.1, 96.6]). SBQ performed well compared to the other questionnaires (sensitivity 75.9% [95% CI 65.0, 84.9], specificity 59.2% [95% CI 56.2, 62.1]). A strategy requiring both SBQ and peak flow to be positive yielded sensitivity of 39.2% (95% CI 28.4, 50.9) and specificity of 97.0% (95% CI 95.7, 97.9). The use of simple screening tests was feasible within the Brazilian primary care setting. The combination of SBQ and peak flow appeared most efficient, when considering performance of the test, cost and ease of use (costing £1690 (5554 R$) with 26.7 cases detected per 1,000 patients). However, the choice of screening tests depends on the clinical setting and availability of resources.ISRCTN registration number: 11377960.

Matteucinol combined with temozolomide inhibits glioblastoma proliferation, invasion, and progression: an in vitro, in silico, and in vivo study.

Glioblastoma is the most prevalent and malignant brain tumor identified in adults. Surgical resection followed by radiotherapy and chemotherapy, mainly with temozolomide (TMZ), is the chosen treatment for this type of tumor. However, the average survival of patients is around 15 months. Novel approaches to glioblastoma treatment are greatly needed. Here, we aimed to investigate the anti-glioblastoma effect of the combination of matteucinol (Mat) (dihydroxyflavanone derived from Miconia chamissois Naudin) with the chemotherapeutic TMZ in vitro using tumor (U-251MG) and normal astrocyte (NHA) cell lines and in vivo using the chick embryo chorioallantoic membrane (CAM) assay. The combination was cytotoxic and selective for tumor cells (28 µg/mL Mat and 9.71 µg/mL TMZ). Additionally, the combination did not alter cell adhesion but caused morphological changes characteristic of apoptosis in vitro. Notably, the combination was also able to reduce tumor growth in the chick embryo model (CAM assay). The docking results showed that Mat was the best ligand to the cell death membrane receptor TNFR1 and to TNFR1/TMZ complex, suggesting that these two molecules may be working together increasing their potential. In conclusion, Mat-TMZ can be a good candidate for pharmacokinetic studies in view of clinical use for the treatment of glioblastoma.

Matteucinol combined with temozolomide inhibits glioblastoma proliferation, invasion, and progression: an in vitro, in silico, and in vivo study

Glioblastoma is the most prevalent and malignant brain tumor identified in adults. Surgical resection followed by radiotherapy and chemotherapy, mainly with temozolomide (TMZ), is the chosen treatment for this type of tumor. However, the average survival of patients is around 15 months. Novel approaches to glioblastoma treatment are greatly needed. Here, we aimed to investigate the anti-glioblastoma effect of the combination of matteucinol (Mat) (dihydroxyflavanone derived from Miconia chamissois Naudin) with the chemotherapeutic TMZ in vitro using tumor (U-251MG) and normal astrocyte (NHA) cell lines and in vivo using the chick embryo chorioallantoic membrane (CAM) assay. The combination was cytotoxic and selective for tumor cells (28 μg/mL Mat and 9.71 μg/mL TMZ). Additionally, the combination did not alter cell adhesion but caused morphological changes characteristic of apoptosis in vitro. Notably, the combination was also able to reduce tumor growth in the chick embryo model (CAM assay). The docking results showed that Mat was the best ligand to the cell death membrane receptor TNFR1 and to TNFR1/TMZ complex, suggesting that these two molecules may be working together increasing their potential. In conclusion, Mat-TMZ can be a good candidate for pharmacokinetic studies in view of clinical use for the treatment of glioblastoma.

Hyperspectral data as a biodiversity screening tool can differentiate among diverse Neotropical fishes.

Hyperspectral data encode information from electromagnetic radiation (i.e., color) of any object in the form of a spectral signature; these data can then be used to distinguish among materials or even map whole landscapes. Although hyperspectral data have been mostly used to study landscape ecology, floral diversity and many other applications in the natural sciences, we propose that spectral signatures can be used for rapid assessment of faunal biodiversity, akin to DNA barcoding and metabarcoding. We demonstrate that spectral signatures of individual, live fish specimens can accurately capture species and clade-level differences in fish coloration, specifically among piranhas and pacus (Family Serrasalmidae), fishes with a long history of taxonomic confusion. We analyzed 47 serrasalmid species and could distinguish spectra among different species and clades, with the method sensitive enough to document changes in fish coloration over ontogeny. Herbivorous pacu spectra were more like one another than they were to piranhas; however, our method also documented interspecific variation in pacus that corresponds to cryptic lineages. While spectra do not serve as an alternative to the collection of curated specimens, hyperspectral data of fishes in the field should help clarify which specimens might be unique or undescribed, complementing existing molecular and morphological techniques.

Metabolomics and transcriptomics to decipher molecular mechanisms underlying ectomycorrhizal root colonization of an oak tree.

Mycorrhizas are known to have a positive impact on plant growth and ability to resist major biotic and abiotic stresses. However, the metabolic alterations underlying mycorrhizal symbiosis are still understudied. By using metabolomics and transcriptomics approaches, cork oak roots colonized by the ectomycorrhizal fungus Pisolithus tinctorius were compared with non-colonized roots. Results show that compounds putatively corresponding to carbohydrates, organic acids, tannins, long-chain fatty acids and monoacylglycerols, were depleted in ectomycorrhizal cork oak colonized roots. Conversely, non-proteogenic amino acids, such as gamma-aminobutyric acid (GABA), and several putative defense-related compounds, including oxylipin-family compounds, terpenoids and B6 vitamers were induced in mycorrhizal roots. Transcriptomic analysis suggests the involvement of GABA in ectomycorrhizal symbiosis through increased synthesis and inhibition of degradation in mycorrhizal roots. Results from this global metabolomics analysis suggest decreases in root metabolites which are common components of exudates, and in compounds related to root external protective layers which could facilitate plant-fungal contact and enhance symbiosis. Root metabolic pathways involved in defense against stress were induced in ectomycorrhizal roots that could be involved in a plant mechanism to avoid uncontrolled growth of the fungal symbiont in the root apoplast. Several of the identified symbiosis-specific metabolites, such as GABA, may help to understand how ectomycorrhizal fungi such as P. tinctorius benefit their host plants.

Role of the left coronary artery geometry configuration in atherosusceptibility: CFD simulations considering sPTT model for blood.

The achievement of clinically viable methodologies to simulate the hemodynamics in patient-specific coronary arteries is still a major challenge. Therefore, the novelty of this work is attained by the introduction of the viscoelastic property of blood in the numerical simulations, to study the role of the left coronary artery (LCA) geometry configuration in the atherosusceptibility. Apparently healthy patients were used and four different methodologies were tested. The methodology giving the most accurate results at the same time of having the lowest computational time is the one considering the viscoelastic property of blood and computational fluid dynamics. A Pearson correlation analysis was used to highlight relationships between geometric configuration and hemodynamic descriptors based on the simulated wall shear stress (WSS). The left main stem (LMS) has the greatest atherosusceptibility followed by the left anterior descending artery (LAD) since the relative residence time (RRT) average values are 3.81 and 3.70 Pa-1, respectively. The geometric parameters with relevant contribution to directional flow change are the cross-sectional areas, especially the one of LMS segment (ALMS), and the curvature of LMS segment. For LMS and LAD segments, when ALMS increases, blood flow disturbance (r = 0.81 in LMS and r = 0.74 in LAD) and atherosusceptibility (r = 0.84 in LMS and r = 0.85 in LAD) increases. When the LMS curvature decreases, the WSS magnitude (r = 0.80 in LMS and r = 0.83 in LAD) decreases, and disturbance (r=-0.80 in LMS and r=-0.91 in LAD) and atherosusceptibility (r=-0.74 in LMS and r=-0.74 in LAD) increases.

Effects of dietary energy content and source using by-products on carcass and meat quality traits of cull ewes.

In cull ewes, energy supply by time short periods can affect growth, carcass traits, and meat quality. The objective of this study was to evaluate the effect of biscuit bran (BB) and cashew nut bran (CNB) in diets with different total digestible nutrient (TDN) content on animal performance and carcass and meat traits of cull ewes. Twenty Morada Nova cull ewes, with the initial BW of 30.1 ±â€¯3.56 kg, and three years of age were distributed in a completely randomized design into factorial scheme 2 × 2, with two energy sources (BB and CNB) × two levels of TDN. All diets were isoproteic with variations in TDN content increased by 10% (TDN10) and 25% (TDN25) above the recommended requirement for the study category, which was 66.0% TDN. The experimental period lasted 56 days, in which daily intake in relation to metabolic weight and weight performance of the animals was determined. The hot carcass, the cold carcass, commercial cuts, loin eye area, and subcutaneous fat thickness were measured, obtained, or calculated. A sample of the Longissimus lumborum (LL) muscle was used by determination of physical-chemical composition, sensory, and fatty acid (FA) profile analysis. The ANOVA was performed to access the effect of diet and energy level on the characteristics studied, and means were compared by the Turkey and Kruskal Wallis tests at 5% of probability. A higher daily gain weight was observed from TDN25 (P = 0.006). Among by-products, higher nutrient intakes were observed in animals fed with BB diets (P < 0.01), except for crude protein. The same patterns have been observed for live weight, reconstituted half-carcass, higher yield in fat thickness, and internal carcass length. Cashew nut bran produced darker colored meat (P = 0.017) and higher cooking weight loss (P = 0.008). Higher lipid content was observed in animals submitted to diets with CNB and TDN25 (P = 0.001). The internal length of the carcass was higher in animals fed with BB (P = 0.041). All diets did not effect on sensory characteristics (P > 0.05). Total digestible nutrient in 25% above recommended promotes higher weight gain and meat with higher lipid content and less weight loss by cooling. The inclusion of BB, compared to CNB, provides a higher weight of carcasses and better conformation, in addition to lower total lipid content with higher proportion for monounsaturated FAs in meat, providing more attractive features for the consumer market.

REALMS study: real-world effectiveness and safety of fingolimod in patients with relapsing-remitting multiple sclerosis in Portugal.

BACKGROUND: Fingolimod, an oral sphingosine 1-phosphate receptor modulator, is approved by EMA for relapsing-remitting multiple sclerosis (RRMS). OBJECTIVES: To assess the effectiveness and safety of fingolimod in patients with RRMS in real-world clinical practice in Portugal. METHODS: Retrospective, multicentre, non-interventional study, reporting 3 years follow-up of data collected from October 2015 to July 2016. Sociodemographic data and previous treatments at baseline and data regarding disease evolution, including number of relapses, annualised relapse rates (ARR) and Expanded Disability Status Scale (EDSS), were collected. RESULTS: Two-hundred and seventy-five participants were enrolled in the REALMS study. Results showed that the main reason to switch to fingolimod was failure of previous treatment (56.7%) and only 3.6% were naïve patients. In the total population, there was a significant decrease in ARR of 64.6% in the first year of treatment, 79.7% in the second year and 82.3% in the third year, compared with baseline. More than 67.0% of patients had no relapses during the 3 years after switching to fingolimod. EDSS remained stable throughout the study. CONCLUSIONS: Therapy with fingolimod showed a sustained effectiveness and safety over the 3 years, particularly on patients switched from first-line drugs (BRACE). No new safety issues were reported.