Evaluating Surgical Outcomes and Survival in Colon Cancer Patients Over 80 Years Old.

BACKGROUND AND AIMS: In the context of an increasing older population, knowing the surgical outcomes of older patients is of paramount importance to define a comprehensive strategy for colon cancer treatment in these patients. This study aimed to analyze the surgical outcomes and survival of patients over 80 years old undergoing surgery for colon cancer. MATERIALS AND METHODS: This is an observational retrospective longitudinal study of patients over 80 years old with colon cancer diagnosis who underwent surgery for this condition, between 2018 and 2021, in a Portuguese hospital. Demographic and clinical features were characterized. Kaplan-Meier method was used for survival analysis. RESULTS: Out of 90 patients in the study, 41.1% were female. The majority (56.7%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or 0, with a median Charlson Comorbidity Index of 7.0. Tumors were primarily located in the right colon (52.2%) and sigmoid colon (25.6%), with most patients having stage II (35.6%) or stage III (25.5%) disease. Elective surgeries accounted for 73% of procedures, and 80.0% had curative intent, with laparoscopic surgery performed in 66.7% of cases. Only 8.3% of those undergoing curative-intent procedures received adjuvant chemotherapy. Emergent admissions were associated with more advanced cancer stages, higher rates of palliative intent procedures (45.8% versus 10.6%, p < 0.001), and more open surgeries (75.0% versus 9.1%, p < 0.001) when compared to elective procedures. Postoperative mortality was higher in the emergent group (20.8% versus 10.6%), though there was no association between the type of admission and postoperative complications. Median overall survival for all patients was 36.7 (95% CI 28.1 to 45.3) months, with significant differences between curative-intent and palliative surgeries (median of 39.8 (95% CI 32.6 to 47.0) versus 10.6 (95% CI 0.67 to 20.5) months, p = 0.015). The elective group of patients had significantly better overall survival compared to the emergent group (median of 36.7 (95% CI 30.7 to 42.7) versus 11.9 (95% CI 6.0 to 17.8) months, p = 0.01). Among the patients who underwent curative-intent procedures, there were no significant differences in overall or disease-free survival between elective and emergent groups. CONCLUSIONS: Despite the increased complexity of managing older patients, particularly in emergent cases, these findings emphasize the importance of elective, curative-intent surgeries to optimize overall survival. Effective treatment strategies and perioperative management tailored to this age group are essential for improving surgical outcomes and extending survival in elderly colon cancer patients.

Crotoxin induces cytotoxic effects in human malignant melanoma cells in both native and detoxified forms.

Introduction: Melanoma, a highly aggressive skin cancer originating in melanocytes, poses a significant threat due to its metastatic potential. While progress has been made in treating melanoma with targeted therapies and immunotherapies, challenges persist. Crotoxin (CTX), the principal toxin in Crotalus durissus terrificus snake venom, exhibits various biological activities, including anti-tumoral effects across multiple cancers. However, its clinical use is limited by toxicity. Thus, exploring alternatives to mitigate adverse effects is crucial. Methods and Results: This study investigates the antitumoral potential of CTX in its native and in a detoxified form, in melanoma cells. Firstly, we demonstrated that detoxified CTX presented reduced phospholipase activity. Both forms proved to be more cytotoxic to SK-MEL-28 and MeWo melanoma cells than non-tumoral cells. In SK-MEL-28 cells, where cytotoxic effects were more pronounced, native and detoxified CTX induced increased necrosis and apoptosis rates. We also confirmed the apoptosis death demonstrated by the activation of caspase-3 and 7, and the formation of apoptotic bodies. Furthermore, both CTX caused cell cycle arrest at the G2/M phase, interfering with melanoma cell proliferation. Cell migration and invasion were also suppressed by both CTX. These results confirm the antitumoral potential of CTX. Discussion: The maintenance of the antiproliferative effects in the detoxified version, with reduced enzymatic activity often liked to harm effects, supports further studies to identify active parts of the molecule responsible for the interesting effects without causing substantial toxic events, contributing to the future use of CTX-derived drugs with safety and efficacy.

γ-Conglutin Immunoreactivity Is Differently Affected by Thermal Treatment and Gastrointestinal Digestion in Lupine Species.

Lupine is a legume commonly used in human diet as a functional food due to its high nutritional content and important technological properties. However, its consumption can lead to the manifestation of adverse immunological reactions, posing significant health issues in sensitized/allergic patients. This work aims to investigate the effect of food processing combined with simulated gastrointestinal (GI) digestion on the immunoreactivity of lupine γ-conglutin. Model foods of wheat pasta containing 35% of lupine flour (Lupinus albus, L. luteus, and L. angustifolius) were prepared and submitted to a boiling process. The proteins were extracted and their profiles characterized by SDS-PAGE. Simulated GI digestion was performed on thermally treated pasta using the INFOGEST harmonized digestion protocol 2.0. The IgG binding capacity of γ-conglutin was assessed by immunoblotting in non-reducing conditions and indirect ELISA with specific antibodies. Results demonstrate that the boiling treatment affected the immunoreactivity of the three lupine species differently. Simulated GI digestion led to extensive destruction of the protein structure, more significant in the intestinal phase, reducing but not abolishing the IgG affinity to γ-conglutin and its potential presentation to immunocompetent cells. This information can offer valuable insights to the food industry for developing food formulations with reduced allergenic properties.

Correction: Bufalo et al. Human Sensory Neuron-like Cells and Glycated Collagen Matrix as a Model for the Screening of Analgesic Compounds. Cells 2022, 11, 247.

In the original publication [...].

Natural compounds-based nanomedicines for cancer treatment: Future directions and challenges.

Several efforts have been extensively accomplished for the amelioration of the cancer treatments using different types of new drugs and less invasives therapies in comparison with the traditional therapeutic modalities, which are widely associated with numerous drawbacks, such as drug resistance, non-selectivity and high costs, restraining their clinical response. The application of natural compounds for the prevention and treatment of different cancer cells has attracted significant attention from the pharmaceuticals and scientific communities over the past decades. Although the use of nanotechnology in cancer therapy is still in the preliminary stages, the application of nanotherapeutics has demonstrated to decrease the various limitations related to the use of natural compounds, such as physical/chemical instability, poor aqueous solubility, and low bioavailability. Despite the nanotechnology has emerged as a promise to improve the bioavailability of the natural compounds, there are still limited clinical trials performed for their application with various challenges required for the pre-clinical and clinical trials, such as production at an industrial level, assurance of nanotherapeutics long-term stability, physiological barriers and safety and regulatory issues. This review highlights the most recent advances in the nanocarriers for natural compounds secreted from plants, bacteria, fungi, and marine organisms, as well as their role on cell signaling pathways for anticancer treatments. Additionally, the clinical status and the main challenges regarding the natural compounds loaded in nanocarriers for clinical applications were also discussed.

Marine waste derived carbon materials for use as sulfur hosts for Lithium-Sulfur batteries.

Lithium-sulfur batteries are a promising alternative to lithium-ion batteries as they can potentially offer significantly increased capacities and energy densities. The ever-increasing global battery market demonstrates that there will be an ongoing demand for cost effective battery electrode materials. Materials derived from waste products can simultaneously address two of the greatest challenges of today, i.e., waste management and the requirement to develop sustainable materials. In this study, we detail the carbonisation of gelatin from blue shark and chitin from prawns, both of which are currently considered as waste biproducts of the seafood industry. The chemical and physical properties of the resulting carbons are compared through a correlation of results from structural characterisation techniques, including electron imaging, X-ray diffraction, Raman spectroscopy and nitrogen gas adsorption. We investigated the application of the resulting carbons as sulfur-hosting electrode materials for use in lithium-sulfur batteries. Through comprehensive electrochemical characterisation, we demonstrate that value added porous carbons, derived from marine waste are promising electrode materials for lithium-sulfur batteries. Both samples demonstrated impressive capacity retention when galvanostatically cycled at a rate of C/5 for 500 cycles. This study highlights the importance of looking towards waste products as sustainable feeds for battery material production.

Inflammatory and Cardiovascular Biomarkers to Monitor Fabry Disease Progression.

Fabry disease is an invalidating multisystemic disorder affecting α-Galactosidase, a rate-limiting hydrolase dedicated to lipid catabolism. Non-metabolized substrates, such as Globotriaosylceramide and its derivatives trigger the direct or indirect activation of inflammatory events and endothelial dysfunction. In spite of the efficacy demonstrated by enzyme replacement therapy or pharmacological chaperones in delaying disease progression, few studies have analyzed whether these treatments can improve the pro-inflammatory state of FD patients. Therefore, the aim of this work was to assess cytokines and cardiovascular risk-related proteins detectable in plasma from FD patients, whether treated or not with ERT, to evaluate the reliability of these markers in monitoring disease stage and treatment effects. We identified inflammatory and endothelial dysfunction markers (ADAMTS-13, TNF-α, GDF-15, MIP-1ß, VEGFA, MPO, and MIC-1) that cooperate in a common pathway and are increased in FD patients' plasma samples. As shown by the assessment of these proteins over time, they can help to evaluate the risk of higher severity in FD, as well as ERT effects. Even though the analyzed proteins cannot be considered as proper biomarkers due to their non-specificity to FD, taken together they can provide a signature of reference molecules with prognostic value for early diagnosis, and evaluation of disease progression and treatment efficacy, using blood samples.

Clinical profiles and treatment outcomes of outpatients with interstitial lung disease and mechanic's hands: A retrospective and observational cohort.

Idiopathic inflammatory myopathies, especially antisynthetase syndrome, often appear outside of the muscles as interstitial lung disease (ILD). Another typical finding is the presence of mechanic's hands. The aim of the present study was to describe the clinical, functional, tomographic, and serological data of patients with ILD and mechanic's hands and their response to treatment and survival rates. This is a retrospective study of ILD with concurrent myopathy. Among the 119 patients initially selected, 51 had mechanic's hands. All the patients were screened for anti-Jo-1 antibodies. An expanded panel of myopathy autoantibodies was also performed in 27 individuals. Of the 51 patients, 35 had 1 or more antibodies. The most common were anti-Jo-1, anti-PL-7, and anti-PL-12, while of the associated antibodies, anti-Ro52 was present in 70% of the 27 tested individuals. A significant response to treatment was characterized by an increase in predicted forced vital capacity (FVC) of at least 5% in the last evaluation done after 6 to 24 months of treatment. A decrease in predicted FVC of at least 5%, the need for oxygen therapy, or death were all considered treatment failures. All patients were treated with corticosteroids, and 71% with mycophenolate. After 24 months, 18 patients had an increase in FVC, 11 had a decrease, and 22 remained stable. After a median follow-up of 58 months, 48 patients remained alive and three died. Patients with honeycombing on high-resolution chest tomography (log-rank = 34.65; P < .001) and a decrease in FVC ≥5% (log-rank = 18.28, P < .001) had a poorer survival rate. Patients with ILD and mechanic's hands respond well to immunosuppressive treatment.

Trends in primary percutaneous coronary intervention for the treatment of acute coronary ST-elevation myocardial infarction in Latin American countries: insights from the CECI consortium.

Background: ST-elevation myocardial infarction (STEMI) requires revascularization treatment, preferably via primary percutaneous coronary interventions (pPCI). There is a lack of data about contemporary management of STEMI in Latin America. Methods: This was a multicenter, multinational, prospective, and dynamic registry of patients undergoing pPCI in Latin America for STEMI (STEMI/LATAMI Registry) that was carried out in nine centers from five countries (Argentina, Ecuador, Venezuela, Bolivia, and the Dominican Republic) between June 2021 and June 2023. All interventionalists involved in the study were originally trained at the same institution (Centro de Estudios en Cardiología Intervencionista, Buenos Aires, Argentina). The primary objective was to evaluate procedural and in-hospital outcomes of pPCI in STEMI and in-hospital outcome in the Latin America (LATAM) region; as secondary endpoints, we analyzed the following subgroups: differences between pPCI vs. pharmaco-invasive or late presenters, gender, elderly and very elderly patients, cardiogenic shock outcomes, and causes of STEMI. Results: In total, 744 STEMI patients who underwent PCI between June 2021 and June 2023 in five countries (nine centers) in our continent were included; 76.3% had a pPCI, 8.1% pharmaco-invasive PCI, and 15.6% had late STEMI PCI. There were no differences in region or center when we evaluated in-hospital and 30 days of death. The rate of procedural success was 96.2%, and the overall in-hospital mortality rate was 2.2%. In the subgroup of pPCI, mean symptom onset-to-balloon time was 295.3 ± 246 min, and mean door-to-balloon time was 55.8 ± 49.9 min. The femoral approach was chosen in 60.5%. In 3.0% of patients, the left main disease was the culprit artery, with 1.63 ± 1.00 stents per patient (564 drug-eluting stents and 652 bare metal stents), with 34 patients receiving only plain optimal balloon angioplasty. Definitive stent thrombosis was related to the infarct artery as the primary cause of STEMI in 7.5% of patients. The use of assistant mechanical devices was low, at 2.1% in the pPCI group. Women were older, with large numbers in very elderly age (≥90 years), greater mortality, and incidence of spontaneous coronary dissection as a cause of STEMI (p < 0.001, p < 0.001, p < 0.001, and p < 0.003, respectively). Conclusion: In suitable LATAM Centers from low/medium-income countries, this prospective registry in patients with STEMI, PCI performed by well-trained operators has comparable results to those reported in well-developed countries.

Plasma IGFBP-3 and IGFBP-5 levels are decreased during acute manic episodes in bipolar disorder patients.

Introduction: Bipolar disorder (BD) is a recurrent and disabling psychiatric disorder related to low-grade peripheral inflammation and altered levels of the members of the insulin-like growth factor (IGF) family. The aim of this study was to evaluate the plasma levels of IGF-2, insulin-like growth factor-binding protein 1 (IGFBP-1), IGFBP-3, IGFBP-5, IGFBP-7, and inflammatory markers such as tumor necrosis factor α (TNF-α), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1ß (MIP-1ß). Methods: We used the Young Mania Rating Scale (YMRS) to determine the severity of the symptomatology, while proteins were measured by enzyme-linked immunosorbent assay (ELISA). We included 20 patients with BD who suffered a manic episode and 20 controls. Some BD patients (n = 10) were evaluated after a period (17 ± 8 days) of pharmacological treatment. Results: No statistical difference was found in IGF-2, IGFBP-1, IGFBP-7, TNF-α, and MIP-1ß levels. However, IGFBP-3 and IGFBP-5 levels were found to be statistically decreased in BD patients. Conversely, the MCP-1 level was significantly increased in BD patients, but their levels were normalized after treatment. Intriguingly, only IGFBP-1 levels were significantly decreased after treatment. No significant correlation was found between the YMRS and any of the proteins studied either before or after treatment or between IGF proteins and inflammatory markers. Discussion: To some extent, IGFBP-3 and IGFBP-5 might be further explored as potential indicators of treatment responsiveness or diagnosis biomarkers in BD.

Boosting Supercapacitor Efficiency with Amorphous Biomass-Derived C@TiO2 Composites.

Carbon materials are readily available and are essential in energy storage. One of the routes used to enhance their surface area and activity is the decoration of carbons with semiconductors, such as amorphous TiO2, for application in energy storage devices.

Multivariate analysis applied to X-ray fluorescence to assess soil contamination pathways: case studies of mass magnetic susceptibility in soils near abandoned coal and W/Sn mines.

Determining the origin and pathways of contaminants in the natural environment is key to informing any mitigation process. The mass magnetic susceptibility of soils allows a rapid method to measure the concentration of magnetic minerals, derived from anthropogenic activities such as mining or industrial processes, i.e., smelting metals (technogenic origin), or from the local bedrock (of geogenic origin). This is especially effective when combined with rapid geochemical analyses of soils. The use of multivariate analysis (MVA) elucidates complex multiple-component relationships between soil geochemistry and magnetic susceptibility. In the case of soil mining sites, X-ray fluorescence (XRF) spectroscopic data of soils contaminated by mine waste shows statistically significant relationships between magnetic susceptibility and some base metal species (e.g., Fe, Pb, Zn, etc.). Here, we show how qualitative and quantitative MVA methodologies can be used to assess soil contamination pathways using mass magnetic susceptibility and XRF spectra of soils near abandoned coal and W/Sn mines (NW Portugal). Principal component analysis (PCA) showed how the first two primary components (PC-1 + PC-2) explained 94% of the sample variability, grouped them according to their geochemistry and magnetic susceptibility in to geogenic and technogenic groups. Regression analyses showed a strong positive correlation (R2 > 0.95) between soil geochemistry and magnetic properties at the local scale. These parameters provided an insight into the multi-element variables that control magnetic susceptibility and indicated the possibility of efficient assessment of potentially contaminated sites through mass-specific soil magnetism.

Genomic deletion of Bcl6 differentially affects conventional dendritic cell subsets and compromises Tfh/Tfr/Th17 cell responses.

Conventional dendritic cells (cDC) play key roles in immune induction, but what drives their heterogeneity and functional specialization is still ill-defined. Here we show that cDC-specific deletion of the transcriptional repressor Bcl6 in mice alters the phenotype and transcriptome of cDC1 and cDC2, while their lineage identity is preserved. Bcl6-deficient cDC1 are diminished in the periphery but maintain their ability to cross-present antigen to CD8+ T cells, confirming general maintenance of this subset. Surprisingly, the absence of Bcl6 in cDC causes a complete loss of Notch2-dependent cDC2 in the spleen and intestinal lamina propria. DC-targeted Bcl6-deficient mice induced fewer T follicular helper cells despite a profound impact on T follicular regulatory cells in response to immunization and mounted diminished Th17 immunity to Citrobacter rodentium in the colon. Our findings establish Bcl6 as an essential transcription factor for subsets of cDC and add to our understanding of the transcriptional landscape underlying cDC heterogeneity.

Whey Cheeses Containing Probiotic and Bioprotective Cultures Produced with Ultrafiltrated Cow's Whey.

Bovine whey cheese (WC) is a product from southern European countries that presents some challenges: its production process involves high energy inputs; the yield is low; and WC has a short shelf life. The application of ultrafiltration (UF) to bovine whey before manufacture of WC and the employment of protective cultures can reduce these disadvantages. The objective of this research was the production of whey cheeses using ultrafiltrated bovine cheese whey with added probiotics or probiotics plus protective cultures. Three types of WC were produced: control CW without any addition (C); CW with the addition of the probiotic Lactobacillus acidophilus (LA5); and CW with the addition of Lactobacillus acidophilus plus a protective culture containing Lacticaseibacillus paracasei and Lacticaseibacillus rhamnosus (LA5FQ4). The WCs were stored under refrigerated conditions for 28 days. The products with added cultures presented lower pH values and higher titratable acidities when compared to the control. Sample LA5 presented the lowest pH and the highest titratable acidity, while LA5FQ4 presented intermediate values. Slight differences were observed between products regarding color parameters, chiefly resulting from storage time. The samples with added cultures were firmer when compared to the control, with LA5 cheeses showing the highest values at the end of the storage. Lactic acid bacteria (LAB) counts were on the order of log 8-9 CFU/g for the products with added cultures. Lower levels of yeasts and molds were detected on the sample with the protective culture (LA5FQ4), so that by the end of storage they presented counts one log cycle lower than C and LA5. Hence, the beneficial impact of the protective culture on the shelf life of the product is evident. Regarding sensory evaluation, LA5FQ4 cheeses obtained the highest scores for all parameters evaluated. It can be concluded that the use of UF associated with the addition of protective cultures can be very useful to reduce the energy consumption of the manufacturing process, to prolong the shelf life of WC and to improve its sensory properties.

Eugenia uniflora (pitanga) juice as a new alternative vehicle for Limosilactobacillus fermentum ATCC 23271: evaluation of antioxidant and anti-infective effects.

Probiotic-containing foods are among the most appreciated functional foods; however, probiotic-based dairy products cannot be consumed by people who are lactose intolerant, allergic to milk, or vegetarian or vegan individuals. Thus, new non-dairy matrices have been tested for probiotics delivery. This study evaluated the growth and viability of Limosilactobacillus fermentum ATCC 23271 and Lacticaseibacillus rhamnosus ATCC 9595 in Pitanga juice (Eugenia uniflora L.). The effects of the fermentation on the antioxidant and anti-infective properties of the juice were also analyzed. The E. uniflora juice allowed lactobacilli growth without supplementation, reaching rates around 8.4 Log CFU/mL and producing organic acids (pH values < 4) after 72 h of fermentation. The strain remained viable after 35 days of refrigerated storage. Fermentation by these bacteria increases the antioxidant capacity of the juice. The central composite rotational design was employed to evaluate the effects of bacterial inoculum and pulp concentration on growth and organic acids production by L. fermentum ATCC 23271. The strain was viable and produced organic acids in all tested combinations. L. fermentum-fermented juice and its cell-free supernatant significantly increased the survival of Tenebrio molitor larvae infected by enteroaggregative Escherichia coli 042. The results obtained in this study provide more insights into the potential of Pitanga juice to develop a functional non-dairy probiotic beverage with antioxidant and anti-infective properties.

An evaluation of treatment response and remission definitions in adult obsessive-compulsive disorder: A systematic review and individual-patient data meta-analysis.

INTRODUCTION: Expert consensus operationalized treatment response and remission in obsessive-compulsive disorder (OCD) as a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) reduction ≥35% and score ≤12 with ≤2 on Clinical Global Impressions Improvement (CGI-I) and Severity (CGI-S) scales, respectively. However, there has been scant empirical evidence supporting these definitions. METHODS: We conducted a systematic review and an individual participant data meta-analysis of randomized-controlled trials (RCTs) in adults with OCD to determine optimal Y-BOCS thresholds for response and remission. We estimated pooled sensitivity/specificity for each percent reduction threshold (response) or posttreatment score (remission) to determine response and remission defined by a CGI-I and CGI-S ≤ 2, respectively. RESULTS: Individual participant data from 25 of 94 eligible RCTs (1235 participants) were included. The optimal threshold for response was ≥30% Y-BOCS reduction and for remission was ≤15 posttreatment Y-BOCS. However, differences in sensitivity and specificity between the optimal and nearby thresholds for response and remission were small with some uncertainty demonstrated by the confidence ellipses. CONCLUSION: While the empirically derived Y-BOCS thresholds in our meta-analysis differ from expert consensus, given the predominance of data from more recent trials of OCD, which involved more refractory participants and novel treatment modalities as opposed to first-line therapies, we recommend the continued use of the consensus definitions.

The Potential of Acorn Extract Treatment on PUFAs Oxidative Stability: A Case Study on Fish Cooking Wastewater.

Fish byproducts are valuable sources of Ω-3 polyunsaturated fatty acids (PUFAs). Their valorization potentially alleviates pressure on this sector. This study uses a circular economy approach to investigate the oil fraction from sardine cooking wastewater (SCW). Analysis of its fatty acid (FA) profile revealed promising PUFA levels. However, PUFAs are highly susceptible to oxidation, prompting the exploration of effective and natural strategies to replace synthetic antioxidants and mitigate their associated risks and concerns. An antioxidant extract from acorn shells was developed and evaluated for its efficacy in preventing oxidative degradation. The extract exhibited significant levels of total phenolic compounds (TPC: 49.94 and 22.99 mg TAE or GAE/g DW) and antioxidant activities (ABTS: 72.46; ORAC: 59.60; DPPH: 248.24 mg TE/g DW), with tannins comprising a significant portion of phenolics (20.61 mg TAE/g DW). LC-ESI-UHR-QqTOF-MS identified ellagic acid, epicatechin, procyanidin B2 and azelaic acid as the predominant phenolic compounds. The extract demonstrated the ability to significantly reduce the peroxide index and inhibit PUFA oxidation, including linoleic acid (LA), eicosapentaenoic (EPA), and docosahexaenoic acid (DHA). This approach holds promise for developing stable, functional ingredients rich in PUFAs. Future research will focus on refining oil extraction procedures and conducting stability tests towards the development of specific applications.