Thoracic aortic aneurysms, a single center's 10-years experience and analysis of outcomes.

INTRODUCTION: Thoracic aortic aneurysms (TAAs) are an increasingly prevalent pathology with significant associated morbidity and mortality. Thoracic endovascular aortic repair (TEVAR) is the primary line of treatment. The purpose of this study was to analyse a single center's experience in the treatment of TAAs and identify possible risk factors for worse outcomes. METHODS: A retrospective review of our institutional database was done to identify all patients treated for TAAs in a 10-year period, from 1 January 2012 to 31 December 2022. Data were extracted from patients' medical records. Primary outcome was all-cause mortality and secondary outcomes were procedure related morbidity (vascular access complications, medullary ischaemia, stroke, endoleaks, migration, aneurysm sac enlargement >5 mm) and need for reintervention at 1-, 6- and 12-month follow-up. A descriptive and inferential analysis of the data was performed. Statistical analyses were conducted using the IBM Statistical Package for Social Sciences (SPSS) software. RESULTS: We identified 34 patients treated for TAAs in this period. Mean age was 68 years [47-87] and 79.4% of patients were male. Mean aneurysm diameter was 63 mm [35-100], 55.9% fusiform and 44.1% saccular. The majority (91.2%) were located at the descending thoracic aorta and 3 (8.8%) of them extended to the aortic arch. The most common aetiology was degenerative in 22 patients (64.7%), followed by aortic dissection in 8 patients (23.5%). Elective surgery was performed in 19 (61.3%) patients and 12 (38.7%) had urgent repair. TEVAR was the treatment of choice in 24 (77.4%) patients, and the remaining 7 (22.6%) were treated with hybrid surgery. Mean length of hospital stay was 10 days [2-80] (6 days for elective repair versus 16 days for urgent repair, p = .016). Follow-up period ranged from 1 month to 10 years. At 1 year follow-up, all-cause mortality was 15%, morbidity was 30% (with 6 (22%) patients having a type Ia endoleak) and need for reintervention was 22%. Aneurysm diameter was a significant risk factor for procedure related morbidity (median diameter of 73.5 mm versus 56.0 mm in patients with no morbidity; p = .027). The presence of type Ia endoleak was significantly associated with higher reintervention rates (p = .001), but not with higher mortality rates (p = .515). Age, female sex, aetiology and urgent repair weren't associated with any significant differences in the outcomes. CONCLUSIONS: TEVAR proved to be effective in the treatment of TAAs, with good outcomes at short and mid-term follow-up. TAAs should be diagnosed earlier and be promptly treated when meeting criteria to prevent worse outcomes.

Infected Thrombosed Popliteal Artery Aneurysm With Cutaneous Fistula.

Introduction: Popliteal artery aneurysms (PAAs) pose some challenges in their surgical management and are often treated by exclusion and bypass procedures. However, post-operative complications, such as endoleaks and sac growth, can occur, potentially leading to serious consequences. Endoleaks, characterised by persistent flow within the aneurysm sac after repair, can cause sac expansion, increasing the risk of adverse outcomes, including the formation of cutaneous fistulae, a rare but potentially severe complication. Report: A 75 year old male with a history of previous bilateral PAA exclusion with a left femoropopliteal bypass using reversed great saphenous vein (GSV) graft in 2012 and a right femoropopliteal bypass using a PTFE prosthesis in 2017, both through medial approach, presented with pain and ulceration in the left popliteal region. Previous angiography had shown residual arterial flow through collateral vessels, requiring thrombin injection. Bilateral bypass thrombosis had also occurred after discontinuing anticoagulation. Computed tomography angiography confirmed a complicated excluded left popliteal aneurysm with superinfection. The patient underwent elective surgery, involving partial aneurysmectomy, endoaneurysmorrhaphy, and fistulectomy through a posterior approach. Post-operatively, the patient experienced resolution of symptoms and inflammatory signs. Discussion: The optimal approach for treating PAAs remains a subject of debate, with some experts advocating the posterior approach to prevent sac growth. However, others support the medial approach, reporting satisfactory results. In this case, the medial approach resulted in incomplete exclusion, leading to sac expansion and a cutaneous fistula. Timely re-intervention through the posterior approach successfully resolved the complication. This report highlights a rare but serious complication of incomplete PAA exclusion. Vigilant post-operative surveillance and intervention are crucial to manage such cases effectively. Further research is warranted to determine the optimal approach for PAA repair and prevent associated complications.

Aneurysmal Degeneration of the Brachial Artery Following Chronic Arteriovenous Fistula Ligation.

Introduction: Arteriovenous fistulas (AVF) are currently considered to be the best vascular access option for patients with end stage chronic kidney disease requiring haemodialysis. In rare cases of patients with chronic AVF, thrombosis or ligation of the access can lead to the development of brachial artery aneurysms. Despite being uncommon, reports of this phenomenon have arisen in recent decades due to an increase in the number of patients undergoing dialysis worldwide. This case presented with a brachial aneurysm that developed after AVF ligation. Case report: A 62 year old male presented to the emergency department with swelling of the medial aspect of his left arm associated with pain, inflammatory signs, and finger paraesthesia. Swelling had started two months previously but had worsened within the last week. He had history of kidney transplant 20 years ago and a chronic functioning radiocephalic fistula that had not been used since, and which had been ligated in the past year due to the development of venous aneurysms. Physical examination revealed a pulsatile mass in his left arm and absent radial and ulnar pulses, without signs of hand ischaemia. There was significant venous collateralisation of the arm and chest and numbness of the left fingers, suggesting venous and neurological compression. Computed tomography angiography showed a large left brachial artery aneurysm (108 x 87 x 180 mm). The patient underwent aneurysm sac emptying and collateral ligation followed by great saphenous vein interposition, with clinical improvement. Conclusion: The presence of a chronic AVF can lead to progressive changes in the arterial wall. Sudden ligation or thrombosis of a functioning AVF causes increased blood pressure within the artery, which may further contribute to its aneurysmal degeneration. In addition, immunosuppressive therapy following kidney transplant has been described as a synergistic risk factor leading to aneurysm formation. Despite being a rare complication, patients with a chronic AVF should be monitored closely after vascular access ligation.

Coral Reef Aorta: Literature Review and Analysis of the Published Cases in the Last 20 Years.

BACKGROUND: Coral reef aorta (CRA) is defined by the presence of heavily calcified exophytic plaques that protrude into the aortic lumen. However, the exact causes and development of this condition are still not fully understood. When the aortic branches are affected, it can result in various symptoms. Despite ongoing research, there is currently no established consensus on the best treatment for CRA. This review aims to examine the latest findings regarding the clinical presentation and approach to treating patients with CRA. METHODS: We conducted a systematic electronic search of the literature using the PubMed and Embase databases. Throughout the search, we adhered to the guidelines outlined in the PRISMA framework. From the identified publications, we extracted information pertaining to patients' characteristics, symptoms, and types of treatment from a total of 124 cases reported over the past 20 years. The primary focus of our analysis was to assess the improvement of signs and symptoms, as well as to evaluate any postoperative complications. To achieve this, we performed both descriptive and inferential analyses on the collected data. Additionally, we conducted subgroup analyses based on treatment types and symptoms observed at presentation, presenting the findings in the form of odds ratios (ORs). RESULTS: After removing duplicate articles, we carefully screened the titles of 67 retrieved articles and excluded those that did not align with the purpose of our study. Subsequently, we thoroughly analyzed the remaining 41 articles along with their references, ultimately including 29 studies that were deemed most relevant for our systematic review. We examined a total of 124 cases of patients diagnosed with CRA, comprising 77 (62.1%) females and 48 (38.7%) males, with a mean age of 59 years (range: 37-84). The predominant signs and symptoms observed were intermittent claudication, reported in 57 (46.0%) patients, followed by refractory hypertension in 45 (36.3%) patients, intestinal angina in 28 (22.6%) patients, and renal insufficiency in 15 (12.1%) patients. Among the treated patients, 110 (88.7%) underwent open surgery repair (OSR), 11 (8.9%) received endovascular treatment, and 3 (2.4%) underwent laparoscopy. Postoperatively, a significant number of patients experienced substantial relief or complete resolution of their symptoms, as well as improved control of hypertension and renal function. In the group of patients treated with OSR, the inhospital stay mortality rate was 10.9%, the morbidity rate was 28.2%, and the reintervention rate was 15.5%. The high mortality rate during hospital stays in this group may be associated with such invasive procedures performed on patients who have substantial cardiovascular burden and multiple comorbidities. Conversely, no postoperative complications were reported in the group of patients treated with endovascular procedures or laparoscopic surgery. CONCLUSIONS: While coral reef aorta (CRA) is considered a rare condition, it is crucial for the medical community to remain vigilant about its diagnosis, particularly in patients presenting with symptoms such as intermittent claudication, refractory hypertension, renal impairment, or intestinal angina. Based on the findings of this review, both OSR and endovascular treatment have shown promise as viable therapeutic options. Although endovascular therapies may not always be feasible or may have reduced durability in these calcified bulky lesions, they should be considered in patients with multiple comorbidities, due to the high postoperative mortality rates associated with more invasive approaches. Additionally, these endoluminal procedures have demonstrated good patency rates during the 18-month follow-up period. It is essential to emphasize that the treatment strategy should be determined on a case-by-case basis, involving a multidisciplinary team to tailor it to the specific needs of each individual patient.

Characterising people with focal drug-resistant epilepsy: A retrospective cohort study.

OBJECTIVES: To describe the demographics, clinical characteristics, drug treatment outcomes, healthcare resource utilization, and injuries among people with focal drug-resistant epilepsy (F-DRE) analysed separately for six European countries. METHODS: We used electronic medical record data from six European (Belgium, Spain, Italy, France, UK and Germany) primary care/specialist care databases to identify antiseizure medication (ASM) treatment-naïve people (aged ≥ 18 years at F-DRE diagnosis). They were followed from their epilepsy diagnosis until death, the date of last record available, or study end. We used descriptive analyses to characterise the F-DRE cohort, and results were reported by country. RESULTS: One-thousand-seventy individuals with F-DRE were included (mean age 52.5 years; 55.4 % female). The median follow-up time from the first diagnosis to the end of the follow-up was 95.5 months across all countries. The frequency of F-DRE diagnosis in 2021 ranged from 8.8 % in Italy to 18.2 % in Germany. Psychiatric disorders were the most common comorbidity across all countries. Frequently reported psychiatric disorders were depression (26.7 %) and anxiety (11.8 %). The median time from epilepsy diagnosis to the first ASM failure ranged from 5.9 (4.2-10.2) months in France to 12.6 (5.8-20.4) months in Spain. Levetiracetam and lamotrigine were the most commonly used ASM monotherapies in all countries. Consultation with a general practitioner is sought more frequently after F-DRE diagnosis than after epilepsy diagnosis, except in the UK. SIGNIFICANCE: No one ASM is optimal for all people with F-DRE, and the risks and benefits of the ASM must be considered. Comorbidities must be an integral part of the management strategy and drive the choice of drugs.

Enhancing Health Benefits through Chlorophylls and Chlorophyll-Rich Agro-Food: A Comprehensive Review.

Chlorophylls play a crucial role in photosynthesis and are abundantly found in green fruits and vegetables that form an integral part of our diet. Although limited, existing studies suggest that these photosynthetic pigments and their derivatives possess therapeutic properties. These bioactive molecules exhibit a wide range of beneficial effects, including antioxidant, antimutagenic, antigenotoxic, anti-cancer, and anti-obesogenic activities. However, it is unfortunate that leafy materials and fruit peels often go to waste in the food supply chain, contributing to the prevailing issue of food waste in modern societies. Nevertheless, these overlooked materials contain valuable bioactive compounds, including chlorophylls, which offer significant health benefits. Consequently, exploring the potential of these discarded resources, such as utilizing them as functional food ingredients, aligns with the principles of a circular economy and presents exciting opportunities for exploitation.

Impact of inbreeding and genetic parameter estimates for seminal traits in Lusitano horses.

The objectives of this study were to establish baseline information for seminal traits in Lusitano stallions, to assess the impact of inbreeding, interval between collections and age on semen quality during the breeding and non-breeding seasons, and to estimate the corresponding genetic parameters. A total of 2129 ejaculates by 146 Lusitano stallions used for artificial insemination, obtained from four equine reproduction centers distributed throughout Portugal, over a period of 14 years (2008-2021), were included in the study. The seminal traits analyzed, and the corresponding means and standard deviations, were gel-free volume (56.95 ± 28.76 mL), concentration (186.48 ± 104.68 × 106), motility (64.1 ± 16.9%), total number of spermatozoa (TNS) (9.271 ± 4.956 × 109) and total number of motile spermatozoa per ejaculate (TNMS) (5.897 ± 3.587 × 109). These results are in the normal range of values described for other breeds. In the stallions analyzed, the mean value for the inbreeding coefficient was 7.93 ± 5.29%, and for age it was 12.70 ± 6.83 years. A significant decline in sperm concentration, motility, TNS, and TNMS was observed as inbreeding increased. The season also influenced sperm concentration, motility, TNS and TNMS, with the highest values observed during the breeding season. When considering the impact of age on Lusitano seminal parameters, results showed a nonlinear relationship, with a positive effect until 18 years of age for volume, motility, TNS and TNMS and a negative effect after this age, with a slow decrease. However, age had a markedly negative effect on sperm concentration. The interval between semen collections only affected (P < 0.05) sperm motility, with a regression coefficient of +1.89 ± 2.17% per additional day. Genetic parameters were estimated with an Animal Model, and the estimated heritability (repeatability) was 0.27 (0.35) for volume, 0.02 (0.38) for sperm concentration, 0.24 (0.44) for motility, 0.29 (0.39) for TNS and 0.41 (0.41) for TNMS. These results suggest that it is possible to improve semen quality by selection and that the properties of semen produced by a stallion tend to remain consistent throughout its lifetime. Furthermore, the impact of inbreeding should be taken into consideration when selecting Lusitano stallions for fertility.

Best Medical Treatment in Patients with Asymptomatic Carotid Stenosis: Myth or Reality?

BACKGROUND: Approximately 1.4 million strokes/year causing about 1.1 million deaths annually occur in Europe and 10%-15% of those strokes are result of thromboembolism from a previously significant asymptomatic carotid stenosis (ACS). Medical treatment has improved considerably in the last 15 years; however, its success depends on patient compliance. The aim of our study was to evaluate, in patients with ACS, the implementation and patient adherence to best medical treatment (BMT). Additionally, we sought to determine the "real-world" incidence of cerebrovascular/coronary events in a cohort of nonoperated ACS patients and weighing this risk against surgical complications in patients with ACS undergoing surgical treatment at our Department. METHODS: Patients with ACS ≥ 60% identified by a carotid ultrasound performed at our Department were retrospectively evaluated. Patients selected to BMT were excluded if the follow-up period was inferior to 2 years, as well as patients lost in follow-up, with missing clinical information and submitted to carotid stenting. Patients' data collection was supported by hospital reporting system and data were introduced into a database created for the purpose. Statistical analysis was performed using SPSS-25 software. RESULTS: After exclusion criteria were applied, the last 120 consecutive patients (60 with ACS submitted do carotid endarterectomy and 60 with ACS under BMT) were retrospectively evaluated. Twenty one patients had ipsilateral events for more than 6 months. Most patients had hypertension (n = 107; 89%), dyslipidemia (n = 101; 84%), 40% had diabetes, 33% diagnosed coronary disease, 32% were overweight or obese, and 17% were current smokers. Blood pressure control, normal weight, statin with/without ezetimibe association, and antiaggregant therapy were only achieved in 33 patients and only 5 had additionally low-density lipoprotein levels < 70 mg/dL, hemoglobin A1c < 7%, and were nonsmokers. Of the 60 patients assigned to medical treatment, 3 (5%) had a stroke at 2 years of follow-up, which was fatal in 1 patient. Among patients submitted to carotid endarterectomy, perioperative stroke was documented in 3% of the patients, none of them disabling or fatal. CONCLUSIONS: Although some recent studies report a risk of ipsilateral stroke of only 0.34% per year in patients with ACS ≥ 50% under BMT therapy in our everyday practice strict compliance to medical treatment fails in most patients. In consequence, we think that a "one-size-fits-all" guideline policy may not be appropriate for all patients and the management of specific ACS patients may need to be individualized.

Giant Sac Growth: A Hybrid Approach to Treat a Misdiagnosed Late Type IIIb Endoleak.

Introduction: Endoleaks are a common complication following endovascular aneurysm repair, yet type IIIb are rare, especially with newer devices, and associated with high morbidity due to repressurisation of the sac. As endografts are used in patients with longer life expectancy, late type IIIb endoleaks are to be expected. This is a report of a giant common iliac aneurysm resulting from a misdiagnosed type IIIb endoleak. Report: An 85 year old man with history of right common iliac artery aneurysm, treated in 2003 with an EXCLUDER AAA Endoprosthesis (WL Gore, Flagstaff, AZ, USA) with iliac limb extension into the external iliac artery, presented at the emergency department with abdominal pain, hypotension, and syncope. He had a known endoleak, unsuccessfully treated by relining the right iliac stent graft overlap zones for a suspected type IIIa endoleak (2009), coil embolisation, and computed tomography (CT) guided thrombin injection of the aneurysmatic sac for a type II (2010), none of which managed to treat the cause with continuous aneurysm growth. The patient refused further treatments, but agreed to maintain surveillance. At admission, CT angiography showed common iliac aneurysm (185 × 134 mm) sac rupture without a visible endoleak. Resuscitative endovascular balloon occlusion of the aorta (REBOA) technique was performed to obtain haemodynamic control, then the aneurysm was approached through a midline incision. A type IIIb endoleak was identified due to a fabric tear on the right iliac limb extension. Suture was attempted without success, then relining of the lesion with an Endurant II Limb (Medtronic, Minneapolis, MN, USA) was performed, which managed to repair the endoleak. Discussion: Type IIIb endoleaks are uncommon and underdiagnosed due to fabric defects being too small or leaking intermittently. They can mimic other types of endoleaks and may cause aneurysm growth and rupture. One should consider this type of endoleak if previous treatments for other types were unsuccessful.

Pertuzumab in Combination with Trastuzumab and Docetaxel in the Neoadjuvant Treatment for HER2-Positive Breast Cancer.

Introduction: This study aims to assess safety and effectiveness of pertuzumab in combination with trastuzumab and docetaxel in the neoadjuvant treatment (NeoT) of HER2-positive breast cancer. Methods: Two consecutive retrospective cohorts (n = 94, 2012-2015 and 2015-2017) of adult women with HER2-positive breast cancer, receiving NeoT at the breast clinic in Portugal (IPO-Porto), were followed. All patients had surgery and received trastuzumab as adjuvant therapy. The 2012-2015 cohort received doxorubicin, cyclophosphamide, docetaxel plus trastuzumab, whereas the 2015-2017 cohort was treated with the same protocol plus pertuzumab. Results: The 2012-2015 cohort was older (median 53 years), with locally advanced tumors (48.1%), mostly hormone receptor positive (59.3%). The 2015-2017 cohort was younger (median 43 years) with 60% operable tumors. Pathologic complete response (pCR) improved in the second cohort, while maintaining a good safety profile and tolerability. Clinical staging (p = 0.001) and hormone receptor (p = 0.003) were significant predictors of pCR, but not treatment regimen (p = 0.304). Conclusion: Further research with larger samples and longer follow-up is needed to understand the clinical differences. Clinical effectiveness of treatment should also be measured through overall and progression-free survival.

Brassica oleracea Var italica by-Products Prevent Lipid Accumulation and Cell Death in a Liver Cell Model of Lipid Toxicity.

Obesity, a rising concern in the Eastern world, encompasses several co-morbidities, namely non-alcoholic fatty liver disease (NAFLD). Potential natural-based interventions to decrease the burden of obesity complications are being investigated. Many of the edible parts of plants are not sold for consumption and end up as massive waste, losing nutritional potential. In fact, a sizeable amount of waste is generated within the different steps of the food supply chain, representing a massive loss of both plant material and natural resources. A good example is Brassica by-products (BBPs). The objective of this work was to investigate the effect of three different extracts from broccoli (Brassica oleracea var italica) by-products in an in vitro model of free fatty acid (FFA)-induced lipotoxicity using human hepatoma HepG2 cells. Broccoli leaf, stalk, and inflorescence extracts induced a dose-dependent decrease in the cell viability of HepG2 cells. However, the maximal non-lethal concentrations of leaves, stalks, and inflorescences (10 µg/mL) did not compromise mitochondrial function or neutral lipid accumulation in HepG2 cells. The extracts significantly decreased FFA-induced lipid accumulation in HepG2 cells either in a co-incubation or pre-incubation strategy. The broccoli extracts' capacity to prevent the FFA-induced decrease in catalase activity in HepG2 may explain the observed effects.

Malnutrition, Cancer Stage and Gastrostomy Timing as Markers of Poor Outcomes in Gastrostomy-Fed Head and Neck Cancer Patients.

For percutaneous endoscopic gastrostomy (PEG)-fed head and neck cancer (HNC) patients, risk markers of poor outcomes may identify those needing more intensive support. This retrospective study aimed to evaluate markers of poor outcomes using TNM-defined stages, initial anthropometry [body mass index (BMI), mid-upper arm circumference (MUAC), tricipital skinfold (TSF), mid-arm muscle circumference (MAMC)] and laboratory data (albumin, transferrin, cholesterol), with 138 patients, 42-94 years old, enrolled. The patients had cancer, most frequently in the larynx (n = 52), predominantly stage IV (n = 109). Stage IVc presented a four times greater death risk than stage I (OR 3.998). Most patients presented low parameters: low BMI (n = 76), MUAC (n = 114), TSF (n = 58), MAMC (n = 81), albumin (n = 47), transferrin (n = 93), and cholesterol (n = 53). In stages I, III, IVa, and IVb, MAMC and PEG-timing were major survival determinants. Each MAMC unit increase resulted in 16% death risk decrease. Additional 10 PEG-feeding days resulted in 1% mortality decrease. Comparing IVa/IVb vs. IVc, albumin and transferrin presented significant differences (p = 0.042; p = 0.008). All parameters decreased as severity of stages increased. HNC patients were malnourished before PEG, with advanced cancer stages, and poor outcomes. Initial MAMC, reflecting lean tissue, significantly increases survival time, highlighting the importance of preserving muscle mass. PEG duration correlated positively with increased survival, lowering death risk by 1% for every additional 10 PEG-feeding days, signaling the need for early gastrostomy.

Colonization of intervertebral discs by Cutibacterium acnes in patients with low back pain: Protocol for an analytical study with microbiological, phenotypic, genotypic, and multiomic techniques.

Lumbar disc degeneration (LDD) and low back pain (LBP) are two conditions that are closely related. Several studies have shown Cutibacterium acnes colonization of degenerated discs, but whether and how these finding correlates with LBP is unknown. A prospective study was planned to identify molecules present in lumbar intervertebral discs (LLIVD) colonized by C. acnes in patients with LDD and LBP and correlate them with their clinical, radiological, and demographic profiles. The clinical manifestations, risk factors, and demographic characteristics of participants undergoing surgical microdiscectomy will be tracked. Samples will be isolated and pathogens found in LLIVD will be characterized phenotypically and genotypically. Whole genome sequencing (WGS) of isolated species will be used to phylotype and detect genes associated with virulence, resistance, and oxidative stress. Multiomic analyses of LLIVD colonized and non-colonized will be carried out to explain not only the pathogen's role in LDD, but also its involvement in the pathophysiology of LBP. This study was approved by the Institutional Review Board (CAAE 50077521.0.0000.5258). All patients who agree to participate in the study will sign an informed consent form. Regardless of the study's findings, the results will be published in a peer-reviewed medical journal. Trials registration number NCT05090553; pre-results.

An Incidental Finding Of A Persistent Sciatic Artery - Case Report And Literature Review.

Persistent sciatic artery is a rare anatomic variation due to the lack of regression during fetal development, associated sometimes with abnormalities of the iliofemoral arterial axis and predisposing the patients to aneurysm formation and thromboembolism, which can compromise the limb. In our department, we assisted a 59-year-old male with an acute limb ischemia as result of an incidental finding of a thrombosed persistent sciatic artery aneurysm.

Beneficial Effects of Broccoli (Brassica oleracea var italica) By-products in Diet-induced Obese Mice.

BACKGROUND/AIM: Obesity currently affects the whole world, with greater incidence in high-income countries, with vast economic and social costs. Broccoli harvest generates many by-products equally rich in bioactive compounds with potential anti-obesity effects. This study aimed to evaluate the anti-obesity effects of broccoli by-products flour (BF) in obese mice. MATERIALS AND METHODS: A commercial high-fat diet formulation (representing a Western diet) was used to induce obesity in mice. BF (0.67% or 1.34% weight/weight) was incorporated as a chemoprevention compound into a control and a hypercholesterolemic diet, at two different concentrations, and fed for 14 weeks to C57BL/6J mice. For a therapeutic approach, two groups were fed with the hypercholesterolemic diet for 10 weeks, and then fed with BF-supplemented diets in the last 4 weeks of the study. RESULTS: BF supplementation helped to maintain a lower body weight, reduced adipose tissue accumulation, and enhanced the basal activity of superoxide dismutase and glutathione S-transferase. Although BF supplementation tended to reduce the relative liver weight increased by the Western diet, the differences were not significant. CONCLUSION: BF appears to have a beneficial effect in preventing weight gain and fat accumulation induced by hypercholesterolemic diets.

Maximizing mRNA vaccine production with Bayesian optimization.

Messenger RNA (mRNA) vaccines are a new alternative to conventional vaccines with a prominent role in infectious disease control. These vaccines are produced in in vitro transcription (IVT) reactions, catalyzed by RNA polymerase in cascade reactions. To ensure an efficient and cost-effective manufacturing process, essential for a large-scale production and effective vaccine supply chain, the IVT reaction needs to be optimized. IVT is a complex reaction that contains a large number of variables that can affect its outcome. Traditional optimization methods rely on classic Design of Experiments methods, which are time-consuming and can present human bias or based on simplified assumptions. In this contribution, we propose the use of Machine Learning approaches to perform a data-driven optimization of an mRNA IVT reaction. A Bayesian optimization method and model interpretability techniques were used to automate experiment design, providing a feedback loop. IVT reaction conditions were found under 60 optimization runs that produced 12 g · L-1 in solely 2 h. The results obtained outperform published industry standards and data reported in literature in terms of both achievable reaction yield and reduction of production time. Furthermore, this shows the potential of Bayesian optimization as a cost-effective optimization tool within (bio)chemical applications.

Lifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp® Causes Intestinal Damage, Gut Dysbiosis, and Behavioral Changes in Mice.

RoundUp® (RUp) is a comercial formulation containing glyphosate (N-(phosphono-methyl) glycine), and is the world's leading wide-spectrum herbicide used in agriculture. Supporters of the broad use of glyphosate-based herbicides (GBH) claim they are innocuous to humans, since the active compound acts on the inhibition of enzymes which are absent in human cells. However, the neurotoxic effects of GBH have already been shown in many animal models. Further, these formulations were shown to disrupt the microbiome of different species. Here, we investigated the effects of a lifelong exposure to low doses of the GBH-RUp on the gut environment, including morphological and microbiome changes. We also aimed to determine whether exposure to GBH-RUp could harm the developing brain and lead to behavioral changes in adult mice. To this end, animals were exposed to GBH-RUp in drinking water from pregnancy to adulthood. GBH-RUp-exposed mice had no changes in cognitive function, but developed impaired social behavior and increased repetitive behavior. GBH-Rup-exposed mice also showed an activation of phagocytic cells (Iba-1-positive) in the cortical brain tissue. GBH-RUp exposure caused increased mucus production and the infiltration of plama cells (CD138-positive), with a reduction in phagocytic cells. Long-term exposure to GBH-RUp also induced changes in intestinal integrity, as demonstrated by the altered expression of tight junction effector proteins (ZO-1 and ZO-2) and a change in the distribution of syndecan-1 proteoglycan. The herbicide also led to changes in the gut microbiome composition, which is also crucial for the establishment of the intestinal barrier. Altogether, our findings suggest that long-term GBH-RUp exposure leads to morphological and functional changes in the gut, which correlate with behavioral changes that are similar to those observed in patients with neurodevelopmental disorders.

Bioactive compounds and physical-chemical characteristics of two genotypes of peach trees submitted to nitrogen fertilization

Nitrogen, which is the primary nutrient peach trees need, may affect their fruit quality. Thus, this study aimed at evaluating the effect of nitrogen fertilization on two genotypes of peach trees, regarding their fruit quality, in three consecutive crops. The experiment was carried out in the experimental area that belongs to the Embrapa Clima Temperado, located in Pelotas, Rio Grande do Sul (RS), Brazil, from 2016, 2016, 2017 and 2018. Four doses of nitrogen (0, 60, 120 and 180 Kg ha-1) and two peach tree genotypes ('Cascata 1513' and 'Cascata 1067') were used. For the fruit, we evaluated epidermis color, pulp firmness, epidermis firmness, soluble solids concentration, titratable acidity, concentration of total phenolic compounds, anthocyanins and antioxidant activity. Fruit underwent physical, chemical and bioactive compound analyses. Results showed that the highest dose of nitrogen (180 Kg ha-1) applied to the soil retards fruit ripening, while no application of nitrogen fertilization brings fruit maturation forward. Nitrogen fertilization via soil does not favor anthocyanins in fruit. Doses of 60 and 120 Kg ha-1 of nitrogen are recommended because they lead to improvement in peach color, epidermis firmness and acidity. Peach tree genotypes influence soluble solids, juice pH, phenolic compounds and antioxidant activity of their fruit.