Unwrapping broken tails: Biological and environmental correlates of predation pressure in limbless reptiles.

Studying species interactions in nature often requires elaborated logistics and intense fieldwork. The difficulties in such task might hinder our ability to answer questions on how biotic interactions change with the environment. Fortunately, a workaround to this problem lies within scientific collections. For some animals, the inspection of preserved specimens can reveal the scars of past antagonistic encounters, such as predation attempts. A common defensive behaviour that leaves scars on animals is autotomy, the loss of a body appendage to escape predation. By knowing the collection site of preserved specimens, it is possible to assess the influence of organismal biology and the surrounding environment in the occurrence of autotomy. We gathered data on tail loss for 8189 preserved specimens of 33 snake and 11 amphisbaenian species to investigate biological and environmental correlates of autotomy in reptiles. We applied generalized linear mixed effect models to evaluate whether body size, sex, life-stage, habitat use, activity pattern, biome, tropicality, temperature and precipitation affect the probability of tail loss in limbless reptiles. We observed autotomy in 23.6% of examined specimens, with 18.7% of amphisbaenian and 33.4% of snake specimens showing tail loss. The probability of tail loss did not differ between snakes and amphisbaenians, but it was higher among large-sized specimens, particularly in adults and females. Chance of tail loss was higher for diurnal and arboreal species, and among specimens collected in warmer regions, but it was unaffected by biome, precipitation, and tropicality. Autotomy in limbless reptiles was affected by size-dependent factors that interplay with ontogeny and sexual dimorphism, although size-independent effects of life-stage and sex also shaped behavioural responses to predators. The increase in probability of tail loss with verticality and diurnality suggests a risk-balance mechanism between species habitat use and activity pattern. Although autotomy is more likely in warmer regions, it seems unrelated to seasonal differences in snakes and amphisbaenians activity. Our findings reveal several processes related to predator-prey interactions involving limbless reptiles, demonstrating the importance of scientific collections to unveil ecological mechanisms at different spatio-temporal scales.

Evaluation of Saccharomyces cerevisiae modified via CRISPR/Cas9 as a cellulosic platform microorganism in simultaneously saccharification and fermentation processes.

The nonrenewable character and deleterious effects of fossil fuels foster the need for cleaner and more inexhaustible energy sources, such as bioethanol. Especially from lignocellulosic biomasses. However, the economic viability of this product in the market depends on process optimization and cost reduction. This research applied a sequential experimental project to investigate the process of enzymatic saccharification and simultaneous fermentation to produce ethanol with sugarcane bagasse. The differential of the work was the application of the strain of Saccharomyces cerevisiae AGY001 which was improved by evolutionary engineering to become thermotolerant and by a heterologous expression based on genomic integration by CRISPR/Cas9 to produce endoglucanase and ß-glucosidase (AsENDO-AsBGL). The maximum ethanol yield found was 89% of the maximum theoretical yield (released sugars), obtained at temperature concentrations, sugarcane bagasse and inoculum at 40 °C, 16.5%, and 4.0 g/L, respectively (12.5 FPU/g bagasse). The mathematical model obtained can predict approximately 83% of the data set with 95% confidence. Therefore, these findings demonstrated the potential of sugarcane bagasse and S. cerevisiae AGY001 strain (CRISPR/Cas9 modified) in bioethanol production without the need for impractical selection media on an industrial scale, in addition to providing useful insights for the development of SSF processes.

Immobilization of Serratia plymuthica by ionic gelation and cross-linking with transglutaminase for the conversion of sucrose into isomaltulose.

Isomaltulose is an alternative sugar obtained from sucrose using some bacteria producing glycosyltransferase. This work aimed to optimize conditions for the immobilization of Serratia plymuthica through ionic gelation and cross-linking by transglutaminase using the sequential experimental strategy for the conversion of sucrose into isomaltulose. The effect of five variables (concentrations of cell mass, alginate, gelatin, transglutaminase, and calcium chloride) was studied, as well as the interactions between them on the matrix composition for the S. plymuthica immobilization. Three experimental designs were used to optimize the concentrations of each variable to obtain higher concentration of isomaltulose. A high conversion of sucrose into isomaltulose (71.04%) was obtained by the cells immobilized in a matrix composed of alginate (1.7%), CaCl2 (0.25 mol/L), gelatin (0.5%), transglutaminase (3.5%) and cell mass (33.5%). As a result, the transglutaminase application as a cross-linking agent improved the immobilization of Serratia plymuthica cells and the conversion of sucrose into isomaltulose.

Cholesteryl ester transfer protein (CETP), HDL capacity of receiving cholesterol and status of inflammatory cytokines in patients with severe heart failure.

BACKGROUND: Heart failure (HF) courses with chronic inflammatory process and alterations in lipid metabolism may aggravate the disease. The aim was to test whether the severity of HF, using brain natriuretic peptide (BNP) as a marker, is associated with alterations in functional aspects of HDL, such as lipid transfer, cholesterol ester transfer protein (CETP) and lecithin-cholesterol acyltransferase (LCAT) concentration. METHODS: Twenty-five HF patients in NYHA class I/II and 23 in class III/IV were enrolled. Plasma lipids, apolipoproteins, CETP, LCAT, oxidized-LDL (oxLDL) and paraoxonase-1 (PON-1) activity were determined. Lipid transfer from a donor artificial nanoparticle to HDL was measured by in vitro assay. RESULTS: Total cholesterol (p = 0.049), LDL-C (p = 0.023), non-HDL-C (p = 0.029) and CETP, that promotes lipid transfer among lipoproteins (p = 0.013), were lower in III/IV than in I/II group. Triglycerides, HDL-C, apo A-I, apo B, oxLDL, LCAT, enzyme that catalyzes serum cholesterol esterification, PON-1 activity, and in vitro transfers of cholesterol, triglycerides and phospholipids to HDL, important steps in HDL metabolism, were equal. IL-8 was higher in III/IV (p = 0.025), but TNFα, IL-1ß, IL-6 and MCP-1 were equal. BNP was negatively correlated with CETP (r = - 0.294; p = 0.042) and positively correlated with IL-8 (r = 0.299; p = 0.039). CONCLUSIONS: Our results disclosed the relationship between CETP levels and HF severity, by comparing two HF groups and by correlation analysis. Lower CETP levels may be a marker of HF aggravation and possibly of worse prognosis. Practical applications of this initial finding, as the issue whether CETP could be protective against HF aggravation, should be explored in larger experimental and clinical studies.

mRNA levels of low-density lipoprotein receptors are overexpressed in the foci of deep bowel endometriosis.

STUDY QUESTION: Is mRNA expression of LDL receptors altered in deep bowel endometriotic foci? SUMMARY ANSWER: mRNA expression of LDL receptors is up-regulated in deep bowel endometriotic foci of patients with endometriosis. WHAT IS KNOWN ALREADY: Several studies have demonstrated the overexpression of low-density lipoprotein receptors in various tumour cell lines and endometriosis has similar aspects to cancer, mainly concerning the pathogenesis of both diseases. This is the first study we know of to investigate lipoprotein receptors expression in deep endometriosis with bowel involvement. STUDY DESIGN, SIZE, DURATION: During 2014-2015, an exploratory case-control study was conducted with 39 patients, including 20 women with a histological diagnosis of deep endometriosis compromising the bowel and 19 women without endometriosis who underwent laparoscopic tubal ligation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Peripheral blood samples were collected on the day of surgery for lipid profile analysis, and samples of endometrial tissue and of bowel endometriotic lesions were also collected. The tissue samples were sent for histopathological analysis and for LDL-R and LRP-1 gene expression screening using quantitative real-time PCR. MAIN RESULTS AND THE ROLE OF CHANCE: Patients with deep endometriosis had lower LDL-cholesterol than patients without the disease (119 ± 23 versus 156 ± 35; P = 0.001). Gene expression analysis of LDL receptors revealed that LDL-R was more highly expressed in endometriotic lesions when compared to the endometrium of the same patient but not more than in the endometrium of women without endometriosis (0.027 ± 0.022 versus 0.012 ± 0.009 versus 0.019 ± 0.01, respectively; P < 0.001). LRP-1 was more highly expressed in endometriotic lesions, both when compared with the endometrium of the same patient and when compared with the endometrium of patients without the disease (0.307 ± 0.207 versus 0.089 ± 0.076 and versus 0.126 ± 0.072, respectively; P < 0.001). The study also showed that LDL-R gene expression in the endometrium of women with endometriosis was higher during the secretory phase of the menstrual cycle (P = 0.001). LRP-1 gene expression was increased during the secretory phase in the endometrium of women without the disease (P = 0.008). LIMITATIONS, REASONS FOR CAUTION: In the endometriotic lesions, the presence of fibrosis is substantial, restricting access to the stromal and glandular components of the lesion. Despite that, we found that LDL receptor mRNA was overexpressed. Future studies may perform laser microdissection to isolate the area of interest in the target tissue, excluding fibrosis contamination. WIDER IMPLICATIONS OF THE FINDINGS: This study supports the feasibility of LDL-R targeted therapy in the treatment of deep endometriosis. STUDY FUNDING/COMPETING INTERESTS: This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP #2011/17245-0). The authors have no conflicts of interest to declare.

Non-animal protein hydrolysates from agro-industrial wastes: A prospect of alternative inputs for cultured meat.

In light of the growing demand for alternative protein sources, laboratory-grown meat has been proposed as a potential solution to the challenges posed by conventional meat production. Cultured meat does not require animal slaughter and uses sustainable production methods, contributing to animal welfare, human health, and environmental sustainability. However, some challenges still need to be addressed in cultured meat production, such as the use of fetal bovine serum for medium supplementation. This ingredient has limited availability, increases production costs, and raises ethical concerns. This review explores the potential of non-animal protein hydrolysates derived from agro-industrial wastes as substitutes for critical components of fetal bovine serum in cultured meat production. Despite the lack of standardization of hydrolysate composition, the potential benefits of this alternative protein source may outweigh its disadvantages. Future research holds promise for increasing the accessibility of cultured meat.

Sustainable synthesis pathways: Bacterial nanocellulose from lignocellulosic biomass for circular economy initiatives.

The hydrothermal pretreatment process stands out as a pivotal step in breaking down the hemicellulosic fraction of lignocellulosic biomasses, such as sugarcane bagasse and eucalyptus sawdust. This pretreatment step is crucial for preparing these materials for subsequent processes, particularly in food applications. This technique aims to disintegrate plant wall components like cellulose, hemicellulose, and lignin, and facilitating access in later phases such as enzymatic hydrolysis, and ultimately making fermentable sugars available. In this study, sugarcane bagasse and eucalyptus sawdust biomass underwent hydrothermal pretreatment at specific conditions, yielding two key components: dry biomass and hemicellulose liquor. The primary focus was to assess the impact of hydrothermal pretreatment followed by enzymatic hydrolysis, using the Celic Ctec III enzyme cocktail, to obtain fermentable sugars. These sugars were then transformed into membranes via strain Gluconacetobacter xylinus bacterial biosynthesis. Notably, the addition of a nitrogen source significantly boosted production to 14.76 g/ in hydrolyzed sugarcane bagasse, underscoring its vital role in bacterial metabolism. Conversely, in hydrolyzed eucalyptus, nitrogen source inclusion unexpectedly decreased yield, highlighting the intricate interactions in fermentation media and the pivotal influence of nitrogen supplementation. Characterization of membranes obtained in synthetic and hydrolyzed media through techniques such as FEG-SEM, FTIR, and TGA, followed by mass balance assessment, gauged their viability on an industrial scale. This comprehensive study aimed not only to understand the effects of pretreatment and enzymatic hydrolysis but to also evaluate the applicability and sustainability of the process on a large scale, providing crucial insights into its feasibility and efficiency in practical food-related scenarios, utilizing nanocellulose bacterial (BNC) as a key component.

Primary results of the brazilian registry of atherothrombotic disease (NEAT).

There is limited contemporary prospective real-world evidence of patients with chronic arterial disease in Latin America. The Network to control atherothrombosis (NEAT) registry is a national prospective observational study of patients with known coronary (CAD) and/or peripheral arterial disease (PAD) in Brazil. A total of 2,005 patients were enrolled among 25 sites from September 2020 to March 2022. Patient characteristics, medications and laboratorial data were collected. Primary objective was to assess the proportion of patients who, at the initial visit, were in accordance with good medical practices (domains) for reducing cardiovascular risk in atherothrombotic disease. From the total of patients enrolled, 2 were excluded since they did not meet eligibility criteria. Among the 2,003 subjects included in the analysis, 55.6% had isolated CAD, 28.7% exclusive PAD and 15.7% had both diagnoses. Overall mean age was 66.3 (± 10.5) years and 65.7% were male patients. Regarding evidence-based therapies (EBTs), 4% were not using any antithrombotic drug and only 1.5% were using vascular dose of rivaroxaban (2.5 mg bid). Only 0.3% of the patients satisfied all the domains of secondary prevention, including prescription of EBTs and targets of body-mass index, blood pressure, LDL-cholesterol, and adherence of lifestyle recommendations. The main barrier for prescription of EBTs was medical judgement. Our findings highlight that the contemporary practice does not reflect a comprehensive approach for secondary prevention and had very low incorporation of new therapies in Brazil. Large-scale populational interventions addressing these gaps are warranted to improve the use of evidence-based therapies and reduce the burden of atherothrombotic disease.ClinicalTrials.gov NCT04677725.

Use of paclitaxel carried in solid lipid nanoparticles to prevent peritoneal fibrosis in rats.

BACKGROUND: Progressive fibrous thickening of peritoneal membrane (PM) is a major complication of long-term peritoneal dialysis. TGF-ß/SMAD pathway activation, inflammation and neoangiogenesis have an important role in PM changes induced by peritoneal dialysis. Here, we investigated the effects of paclitaxel (PTX) carried in lipid core nanoparticles (LDE) on the development of peritoneal fibrosis (PF) in rats. METHODS: To induce PF, 21 male Wistar rats (300-350g) were injected with chlorhexidine gluconate for 15 consecutive days and randomly assigned to three groups: 1)PF, n = 5: no treatment; 2)LDE, n = 8: treated with LDE only, 3/3 days during 15 days; 3)LDE-PTX, n = 8: treated with PTX (4mg/kg) associated with LDE, 3/3 days during 15 days. A Control group without PF induction (n = 5) was designed, received saline solution, 3/3 days. Peritoneum function tests were performed, and anterior abdominal wall samples of the PM were collected for analyses of peritoneal thickness, immunohistochemitry, and gene expression. RESULTS: LDE-PTX treatment preserved the membrane function, maintaining the ultrafiltration rate and mass transfer of glucose at normal levels. LDE-PTX also prevented PM thickening induced by chlorhexidine gluconate injections. LDE-PTX treatment reduced the number of myofibroblasts infiltrating PM and inhibited the cell proliferation. Gene expression of fibronectin, FSP-1, VEGF, TGF-ß, and SMAD3 were reduced by LDE-PTX. CONCLUSIONS: LDE-PTX was effective to prevent development of PF and preserve the PM filtration capacity in this rat model, with clear-cut actions on pro-fibrotic mechanisms. Thus, LDE-PTX can be candidate for future clinical trials as adjuvant to peritoneal dialysis to prevent PF development, since this preparation is devoid of toxicity as shown previously.

Treatment With Methotrexate Associated With Lipid Core Nanoparticles Prevents Aortic Dilation in a Murine Model of Marfan Syndrome.

In Marfan syndrome (MFS), dilation, dissection, and rupture of the aorta occur. Inflammation can be involved in the pathogenicity of aortic defects and can thus be a therapeutic target for MFS. Previously, we showed that the formulation of methotrexate (MTX) associated with lipid nanoparticles (LDE) has potent anti-inflammatory effects without toxicity. To investigate whether LDEMTX treatment can prevent the development of aortic lesions in the MFS murine model. MgΔloxPneo MFS (n = 40) and wild-type (WT, n = 60) mice were allocated to 6 groups weekly injected with IP solutions of: (1) only LDE; (2) commercial MTX; (3) LDEMTX (dose = 1mg/kg) between 3rd and 6th months of life. After 12 weeks of treatments, animals were examined by echocardiography and euthanatized for morphometric and molecular studies. MFS mice treated with LDEMTX showed narrower lumens in the aortic arch, as well as in the ascending and descending aorta. LDEMTX reduced fibrosis and the number of dissections in MFS but not the number of elastic fiber disruptions. In MFS mice, LDEMTX treatment lowered protein expression of pro-inflammatory factors macrophages (CD68), T-lymphocytes (CD3), tumor necrosis factor-α (TNF-α), apoptotic factor cleaved-caspase 3, and type 1 collagen and lowered the protein expression of the transforming growth factor-ß (TGF-ß), extracellular signal-regulated kinases ½ (ERK1/2), and SMAD3. Protein expression of CD68 and CD3 had a positive correlation with an area of aortic lumen (r 2 = 0.36; p < 0.001), suggesting the importance of inflammation in the causative mechanisms of aortic dilation. Enhanced adenosine availability by LDEMTX was suggested by higher aortic expression of an anti-adenosine A2a receptor (A2a) and lower adenosine deaminase expression. Commercial MTX had negligible effects. LDEMTX prevented the development of MFS-associated aortic defects and can thus be a candidate for testing in clinical studies.

Epidemiology of snake envenomation from Mato Grosso do Sul, Brazil.

Snake envenomation is considered a public health problem in tropical countries, where they occur in a high incidence. The present study reports the snake envenomation that occurred in Mato Grosso do Sul state (Brazil) between 2007 and 2017. Epidemiological data were obtained from the online platform of the Notification Disease Information System and were analyzed according to biome. A total of 5568 cases of snake envenomations were recorded during the study period, where the highest frequency was registered between October and April. The majority of envenomations occurred in working-age males (20 to 39 years), caused mainly by Bothrops snakes, and the duration of care after the envenomation in most cases took three hours. The municipalities that showed the highest snake envenomations case per 100,000 inhabitants presents low population density, and have their economy based on agricultural activity, which is a risk factor to snake envenomations. To the Mato Grosso do Sul state, the total number of snake envenomations had a positive relationship with the size of the municipality. Since this, larger areas usually have a mosaic of environments, which may harbor higher richness and abundance of snakes, and can cause more snake encounters with the population, resulting in more snake envenomations.

Noninvasive Neuromodulation Techniques in Difficult Tracheostomy Weaning of Patients With Spinal Cord Injury: Report of Two Cases.

High spinal cord injured patients (SCI) are susceptible to respiratory muscle impairments. Transcranial direct current stimulation (tDCS) and peripheral electrical stimulation (PES) may influence the diaphragm's central control, but until now they are not described as a therapeutic resource for difficult weaning. We present two case reports of SCI patients (P1 and P2) with long-term tracheostomy (>40 days) and hospital stay (>50 days). In association with respiratory exercise, P1 received a combined application of anodal tDCS over the supplementary motor area plus sensory PES in the thoracic-abdominal muscles, and P2 received isolated excitatory PES in the abdominal muscles, applied daily except on weekends. Maximum inspiratory/expiratory pressure, peak cough flow, diaphragm excursion, and thickening fraction were measured in the first and last days of the protocol. Both patients had improvements, with clinical impact such as cough effectiveness, decannulated after 15 applications of stimulation. Augmentation of neural respiratory drive and corticospinal excitability is suggested.

A morphological and molecular study of Hydrodynastes gigas (Serpentes, Dipsadidae), a widespread species from South America.

BACKGROUND: Studies with integrative approaches (based on different lines of evidence) are fundamental for understanding the diversity of organisms. Different data sources can improve the understanding of the taxonomy and evolution of snakes. We used this integrative approach to verify the taxonomic status of Hydrodynastes gigas (Duméril, Bibron & Duméril, 1854), given its wide distribution throughout South America, including the validity of the recently described Hydrodynastes melanogigas Franco, Fernandes & Bentim, 2007. METHODS: We performed a phylogenetic analysis of Bayesian Inference with mtDNA 16S and Cytb, and nuDNA Cmos and NT3 concatenated (1,902 bp). In addition, we performed traditional morphometric analyses, meristic, hemipenis morphology and coloration pattern of H. gigas and H. melanogigas. RESULTS: According to molecular and morphological characters, H. gigas is widely distributed throughout South America. We found no evidence to support that H. gigas and H. melanogigas species are distinct lineages, therefore, H. melanogigas is a junior synonym of H. gigas. Thus, the melanic pattern of H. melanogigas is the result of a polymorphism of H. gigas. Melanic populations of H. gigas can be found in the Tocantins-Araguaia basin.

Applications of Non-invasive Neuromodulation for the Management of Disorders Related to COVID-19.

Background: Novel coronavirus disease (COVID-19) morbidity is not restricted to the respiratory system, but also affects the nervous system. Non-invasive neuromodulation may be useful in the treatment of the disorders associated with COVID-19. Objective: To describe the rationale and empirical basis of the use of non-invasive neuromodulation in the management of patients with COVID-10 and related disorders. Methods: We summarize COVID-19 pathophysiology with emphasis of direct neuroinvasiveness, neuroimmune response and inflammation, autonomic balance and neurological, musculoskeletal and neuropsychiatric sequela. This supports the development of a framework for advancing applications of non-invasive neuromodulation in the management COVID-19 and related disorders. Results: Non-invasive neuromodulation may manage disorders associated with COVID-19 through four pathways: (1) Direct infection mitigation through the stimulation of regions involved in the regulation of systemic anti-inflammatory responses and/or autonomic responses and prevention of neuroinflammation and recovery of respiration; (2) Amelioration of COVID-19 symptoms of musculoskeletal pain and systemic fatigue; (3) Augmenting cognitive and physical rehabilitation following critical illness; and (4) Treating outbreak-related mental distress including neurological and psychiatric disorders exacerbated by surrounding psychosocial stressors related to COVID-19. The selection of the appropriate techniques will depend on the identified target treatment pathway. Conclusion: COVID-19 infection results in a myriad of acute and chronic symptoms, both directly associated with respiratory distress (e.g., rehabilitation) or of yet-to-be-determined etiology (e.g., fatigue). Non-invasive neuromodulation is a toolbox of techniques that based on targeted pathways and empirical evidence (largely in non-COVID-19 patients) can be investigated in the management of patients with COVID-19.

Diferenças demográficas e clínicas em pacientes com suspeita de hipercolesterolemia familiar: uma análise observacional / Demographic and clinical differences in patients with suspected familial hypercholesterolemia: an observational analysis

INTRODUÇÃO: A hipercolesterolemia familiar (HF) é uma doença autossômica dominante, caracterizada por altos níveis plasmáticos do colesterol de lipoproteína de baixa densidade (LDL-C) e pelo alto risco de desenvolvimento prematuro de doenças cardiovasculares (DCV). OBJETIVO: Avaliar as diferentes características demográficas e clínicas em pacientes com suspeita de HF. MÉTODOS: Estudo observacional transversal com 54 pacientes atendidos entre janeiro de 2023 a fevereiro de 2024. Critérios de inclusão: (1) LDL-C > 190 mg/dL e (2) pontuação mínima de 3 pontos no Dutch Lipid Clinic Network (Dutch MEDPED). Dados avaliados: idade, sexo, IMC, presença de hipertensão arterial sistêmica (HAS), diabetes mellitus (DM), tabagismo e história de doença arterial coronariana (DAC). RESULTADOS: A idade média da população estudada foi 56,9 anos, enquanto a média dos maiores níveis de LDL-C durante o acompanhamento foi de 296 mg/dL. Entre os critérios prevalentes observados, destacam-se: mulheres (62,9%, n=34), indivíduos de raça branca (64,8%, n=35), pacientes com HAS (75,9%, n=41) e não fumantes (88,8%, n=48). A prevalência de DAC precoce foi de 48,1% (n=25), com maior representatividade entre as mulheres (64%, n=16). A presença de pacientes diabéticos foi de 31,4% (n=17) e a de obesos foi de 37% (n=20). Na análise dos critérios do Dutch MEDPED, 48,1% (n=26) dos pacientes obtiveram pontuação para o diagnóstico provável de HF, enquanto 31,4% (n=17) tiveram o diagnóstico confirmado e 20,3% (n=11) foram classificados como possíveis casos. DISCUSSÃO/CONCLUSÃO: O destaque do gênero feminino e da maior incidência de DAC nesse grupo ressalta as diferenças observadas na população com HF em relação aos que não possuem esse diagnóstico. As mulheres com HF são diagnosticadas mais tardiamente e permanecem menor tempo em tratamento. As estatinas são contraindicadas na gestação. Desta forma, em períodos de tentativa de concepção, gestação e amamentação permanecem sem tratamento medicamentoso. Esse cenário, somado ao diagnóstico tardio, permitem que esse grupo fique maior tempo exposto a altos níveis de LDL-C ao longo da vida. Dentre os fatores de risco cardiovasculares conhecidos, houve destaque para o número elevado de pacientes obesos. Esse número está bem acima do percentual médio da população brasileira, que é de 26,8%.

Nanotechnology for the treatment of deep endometriosis: uptake of lipid core nanoparticles by LDL receptors in endometriotic foci.

OBJECTIVE: Rapidly dividing cells in multiple types of cancer and inflammatory diseases undergo high low density lipoprotein (LDL) uptake for membrane synthesis, and coupling an LDL-like nanoemulsion, containing lipid nanoparticles (LDE) to a chemotherapeutic agent efficiently targets these cells without significant systemic effects. This was a prospective exploratory study that evaluated the uptake of a radioactively labeled LDE emulsion by receptors of endometriotic foci and the capacity of the LDE for cellular internalization. METHODS: The lipid profile of each patient was determined before surgery, and labeled LDE were injected into fourteen patients with intestinal or nonintestinal endometriosis. The radioactivity of each tissue sample (intestinal endometriosis, nonintestinal endometriosis, healthy peritoneum, or topical endometrium) was measured. RESULTS: The group with intestinal endometriosis presented higher levels of plasma LDL but lower LDE uptake by foci than the nonintestinal group, suggesting less cell division and more fibrosis. The uptake of LDE was highest in the topical endometrium, followed by the healthy peritoneum, and lowest in the endometriotic lesion. Since the endometriotic foci showed significant LDE uptake, there was likely increased consumption of LDL by these cells, similar to cells in cancers and inflammatory diseases. Plasma cholesterol levels had no influence on LDE uptake, which showed that the direct delivery of the nanoemulsion to target tissues was independent of serum lipoproteins. There were no significant differences in the parameters (p>0.01) because of the small sample size, but the findings were similar to those of previous studies. CONCLUSION: Nanotechnology is a promising therapeutic option for surgery and hormonal blockage for deep endometriosis, with a lower complication rate and no systemic side effects.

Aneurisma de ventrículo esquerdo roto e contido: um relato de caso / Left ventricular aneurysm with contained rupture

Relato de caso: Paciente masculino, 70 anos, hipertenso, diabético, dislipidêmico e ex-tabagista. Apresentou infarto agudo do miocárdio com supradesnivelamento do segmento ST de parede anterior, sendo submetido à angioplastia da artéria descendente anterior em julho de 2022. Em setembro de 2022, foi admitido em serviço de emergência de hospital geral com quadro de dor torácica ventilatório-dependente e dispneia. Ao exame físico, seu quadro era estável hemodinamicamente.

Hypertonic Saline Solution Reduces Microcirculatory Dysfunction and Inflammation in a Rat Model of Brain Death.

BACKGROUND: Brain death (BD) induces hemodynamic instability with microcirculatory hypoperfusion, leading to increased organ inflammation and dysfunction. This study investigated the effects of 7.5% hypertonic saline solution (HSS) on mesenteric microcirculatory dysfunction and inflammation in a rat model of BD. METHODS: Male Wistar rats were anesthetized and mechanically ventilated. BD was induced by rapidly inflating an intracranial balloon catheter. The rats were randomly divided into: SH, sham-operated rats subjected to trepanation; NS, rats treated with NaCl 0.9%, 4 mL/kg immediately after BD; T1, rats treated with HSS (NaCl 7.5%, 4 mL/kg) immediately or 60 min after BD, T60. All groups were analyzed 180 min after the start of the experiment. RESULTS: Rats in BD groups presented with a similar hypertensive peak, followed by hypotension. Proportion of perfused small vessels was decreased in the NS group (46%) compared with the SH group (74%, P = 0.0039). HSS restored the proportion of perfused vessels (T1 = 71%, P = 0.0018). The anti-endothelial nitric oxide synthase (eNOS) protein expression significantly increased in rats given HSS (T1, and T60, P = 0.0002). Similar results were observed regarding endothelin-1 (P < 0.0001). Increased numbers of rolling (P = 0.0015) and migrated (P = 0.0063) leukocytes were observed in the NS group compared with the SH group. Rats given HSS demonstrated an overall reduction in leukocyte-endothelial interactions. The ICAM-1 levels increased in the NS group compared with the SH group, and decreased in the HSS-treated groups (P = 0.0002). CONCLUSIONS: HSS may improve the density of mesenteric perfused small vessels due to its effects on eNOS and endothelin-1 protein expression, and reduces inflammation by decreasing leukocyte adhesion and migration in a rat model of BD.

Interações complexas na hipercolesterolemia familiar: um estudo de caso de aterosclerose multivascular e variantes genéticas / Complex interactions in familial hypercholesterolemia: a case study of multivascular atherosclerosis and genetic variants

INTRODUÇÃO: A hipercolesterolemia familiar (HF) é um distúrbio genético bem reconhecido que se manifesta como níveis significativamente elevados de LDL-c sérico devido a aberrações no metabolismo das lipoproteínas. A maioria dos casos de HF, especificamente 85-90%, está associada a mutações patogênicas no gene do receptor de LDL (LDLR). Além disso, a presença de mutações de perda de função (LOF) no gene PCSK9 tem sido associada a um risco reduzido de doença cardiovascular, um fenômeno observado mesmo quando variantes patogênicas de LDLR coexistem. MÉTODOS: Este estudo incluiu um homem de 46 anos com dislipidemia e uso inconsistente de rosuvastatina. Na história familiar consta uma irmã (caso índice) e um sobrinho diagnosticados com HF portadores de variante patogênica de LDLR (c.313+1G>A, heterozigoto). RESULTADOS: O paciente relatou o aparecimento de dor precordial típica um mês antes da consulta. O exame físico revelou arco corneano. Os resultados laboratoriais iniciais mostraram colesterol total em 254 mg/dL, LDL-c em 191 mg/dL, HDL-c em 49 mg/dL e triglicerídeos em 69 mg/dL. Um escore Dutch MedPed de 11 confirmou HF. A ecocardiografia transtorácica indicou função ventricular esquerda normal. A angiografia coronária revelou calcificação significativa e estenose da artéria coronária direita (RCA) e da artéria circunflexa esquerda proximal (LCx). A intervenção incluiu angioplastia LCx e manejo conservador da RCA. Medicamentos pós-alta incluíram AAS 100mg/dia, Clopidogrel 75mg/dia, Rosuvastatina 40mg/ dia e Ezetimibe 10mg/dia. O nível de LDL-c diminuiu para 76 mg/dL no acompanhamento. A análise genética confirmou a variante familiar de LDLR e identificou uma mutação LOF coexistente de PCSK9 (R46L, heterozigoto). CONCLUSÃO: Este caso destaca a gravidade e complexidade da aterosclerose multivascular associada à HF. Embora a variante LOF de PCSK9 seja potencialmente protetora, sua influência nos resultados clínicos permanece incerta. Essa ambiguidade reforça a progressão multifatorial da aterosclerose e a resposta variável ao tratamento em pacientes com HF. Isso ressalta a importância de identificar fatores genéticos e não genéticos adicionais que contribuem para a doença, além dos loci genéticos conhecidos para entender e gerenciar melhor essa condição clínica.

Disjunção do anel mitral e arritmias ventriculares: um diagnóstico diferencial em paciente sob imunoterapia / Mitral annular disjunction and ventricular arrhythmias: a differential diagnosis in a patient undergoing immunotherapy

INTRODUÇÃO: O prolapso da válvula mitral é uma condição relativamente frequente, apresentando uma prevalência de aproximadamente 2% na população. Geralmente, o prognóstico é favorável. Contudo, em uma pequena proporção de pacientes pertencentes às faixas etárias jovens e de meia-idade, observou-se uma associação desse quadro com arritmias ventriculares malignas, principalmente quando ocorre a disjunção anular mitral (DAM). OBJETIVO: Relatar um caso de DAM como causa de arritmias ventriculares, sendo um diagnóstico diferencial de arritmia induzida por imunoterapia. RELATO: Mulher, 48 anos, realizou tratamento de neoplasia de mama com pembrolizumabe. Um ano após, é encaminhada para investigação de palpitação e avaliação quanto à possibilidade de associação do quadro com o imunoterápico. Na anamnese, destacava quadro de palpitação mesmo antes do tratamento oncológico. O eletrocardiograma apresentava ritmo sinusal e presença de 2 extrassístoles ventriculares isoladas. Solicitado Holter de 24h que evidenciou ritmo sinusal e extrassístoles ventriculares de alta incidência. O ecocardiograma não apresentava alterações dignas de nota. À ressonância magnética cardíaca (RMC), átrios e ventrículos direito e esquerdo evidenciaram dimensões e funções preservadas, músculos papilares com hipointensidade em relação ao miocárdio, valva mitral com prolapso, deslocamento sistólico mínimo em direção ao átrio medido 2 mm acima do plano valvar e disfunção do anel mitral, medindo 8 mm. Diante disso, é iniciado terapia com betabloqueador e paciente evoluindo em seguimento ambulatorial, com melhora clínica. Ademais, concluímos que não se trata de uma arritmia induzida pela imunoterapia. DISCUSSÃO: O pembrolizumabe trata-se de uma imunoterapia, classificada como inibidor de checkpoint imunológico (ICI). A cardiotoxicidade dos ICI pode ser agrupada em duas categorias: efeitos adversos inflamatórios (miocardite, pericardite e vasculite) e toxicidade cardiovascular não inflamatória (síndrome Takotsubo-like, disfunção ventricular assintomática não inflamatória e arritmias). Mas, diante dos dados da anamnese e dados da RMC, descartou-se a associação do pembrolizumabe com o quadro clínico. O estudo destaca a importância do Cardio-Oncologista, ao diagnosticar a DAM como causa da arritmia, e a não associação, nesse caso, com o imunoterápico, o que poderia ser relatado como evento adverso.