The Relationship between Lifestyle, Mental Health, and Loneliness in the Elderly during the COVID-19 Pandemic.

The study focused on examining the relationship between well-being and various psychological factors such as loneliness, anxiety, depression, and stress, whilst also considering changes in lifestyle. A total of 108 elderly participants, with an average age of 70.38 years, were enrolled in this quantitative cross-sectional study. The research employed a battery of assessment tools including a Sociodemographic Data Questionnaire, Mini-Mental State Examination, Positive Mental Health Scale, Stress Perception Scale, Geriatric Anxiety Inventory, Geriatric Depression Scale (reduced version), Loneliness Scale, and International Physical Activity Questionnaire. Descriptive analysis was conducted in order to understand the distribution of scores across these variables, followed by the categorization of participants based on the reported alterations in eating and physical activity behaviors. Correlations between variables were assessed using Spearman correlation and an EBIC-LASSO network analysis. The findings indicated a potential detriment to the well-being of elderly individuals practicing social distancing, evidenced by heightened symptoms of loneliness, depression, anxiety, and stress, alongside the reported changes in dietary patterns and physical activity. The study underscores the importance of understanding the pandemic's impact on the well-being of older adults and advocates for longitudinal investigations to delineate the evolving effects of social distancing measures across different phases of the pandemic.

Immune pathway through endometriosis to ovarian cancer.

Endometriosis is an estrogen-dependent inflammatory disease, defined by the presence of functional endometrial tissue outside of the uterine cavity. This disease is one of the main gynecological diseases, affecting around 10%-15% women and girls of reproductive age, being a common gynecologic disorder. Although endometriosis is a benign disease, it shares several characteristics with invasive cancer. Studies support that it has been linked with an increased chance of developing endometrial ovarian cancer, representing an earlier stage of neoplastic processes. This is particularly true for women with clear cell carcinoma, low-grade serous carcinoma and endometrioid. However, the carcinogenic pathways between both pathologies remain poorly understood. Current studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers (EAOCs) via pathways associated with oxidative stress, inflammation, and hyperestrogenism. This article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis, specifically focusing on the complex relationship between the immune response to endometriosis and cancer, including the molecular mechanisms and their ramifications. Examining recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.

Prediction of tuberculosis clusters in the riverine municipalities of the Brazilian Amazon with machine learning.

OBJECTIVE: Tuberculosis (TB) is the second most deadly infectious disease globally, posing a significant burden in Brazil and its Amazonian region. This study focused on the "riverine municipalities" and hypothesizes the presence of TB clusters in the area. We also aimed to train a machine learning model to differentiate municipalities classified as hot spots vs. non-hot spots using disease surveillance variables as predictors. METHODS: Data regarding the incidence of TB from 2019 to 2022 in the riverine town was collected from the Brazilian Health Ministry Informatics Department. Moran's I was used to assess global spatial autocorrelation, while the Getis-Ord GI* method was employed to detect high and low-incidence clusters. A Random Forest machine-learning model was trained using surveillance variables related to TB cases to predict hot spots among non-hot spot municipalities. RESULTS: Our analysis revealed distinct geographical clusters with high and low TB incidence following a west-to-east distribution pattern. The Random Forest Classification model utilizes six surveillance variables to predict hot vs. non-hot spots. The machine learning model achieved an Area Under the Receiver Operator Curve (AUC-ROC) of 0.81. CONCLUSION: Municipalities with higher percentages of recurrent cases, deaths due to TB, antibiotic regimen changes, percentage of new cases, and cases with smoking history were the best predictors of hot spots. This prediction method can be leveraged to identify the municipalities at the highest risk of being hot spots for the disease, aiding policymakers with an evidenced-based tool to direct resource allocation for disease control in the riverine municipalities.

The incidence of osteoradionecrosis of the jaws in oral cavity cancer patients treated with intensity-modulated radiotherapy: a systematic review and meta-analysis.

OBJECTIVE: A systematic review with meta-analysis was conducted to define the incidence of osteoradionecrosis (ORN) in patients with oral cavity cancer (OCC) treated with intensity-modulated radiotherapy (IMRT), and to identify the risk factors influencing its development. STUDY DESIGN: Six databases were searched systematically. A meta-analysis was performed to determine overall, spontaneous, and dental extraction-attributed incidences of ORN. The Grading of Recommendations Assessment, Development, and Evaluation tool evaluated evidence certainty. RESULTS: Out of 11 eligible studies, 6 underwent meta-analysis for the overall aggregated ORN incidence in OCC patients receiving IMRT, resulting in an incidence rate of 8% (95% CI: 6%-11%). Regarding development reasons, 2 studies were assessed, revealing an incidence of 36% (95% CI: 1%-98%) for spontaneous ORN, and 17% (95% CI: 5%-44%) ensued from dental extraction exclusively pre-RT. All rates had very low certainty of evidence. Factors significantly correlated with ORN development included postoperative RT use (78%), employment of therapeutic doses above 50 Gy, and mandibular involvement (80.5%). CONCLUSION: The findings suggest that IMRT alone is not sufficient to decrease ORN rates in OCC patients, underscoring the importance of precisely identifying the involved risk factors. However, further detailed primary studies will be necessary.

"It was unusual but amazing": demand creation for PrEP among adolescents' men who have sex with men (MSM) and transgender women (TGW) in Brazil.

This study aimed to analyze the challenges in demand creation for participation in an HIV pre-exposure prophylaxis (PrEP) project in two Brazilian capitals. This qualitative study was conducted with men who have sex with men and transgender women aged 15 to 19 years who lived in two Brazilian state capitals. For this analysis, 27 semi-structured interviews carried out from 2019 to 2020 were evaluated by reflexive thematic content analysis. For participants, PrEP demand creation was essential for their interaction, mediation, bonding, and attachment and proved effective for PrEP acceptability and adherence. Adolescents' narratives showed that the strategies promoted HIV combination prevention, opened up opportunities for recruitment meetings, helped to negotiate with and convince individuals to use PrEP, strengthened peer education, and evoked a feeling of "being with" and "walking together" despite the challenges. Face-to-face or online interactions using social technologies played a crucial role in recruiting adolescents for the project, expanding knowledge on PrEP and other combination prevention strategies and access to health services and self-care.

The Role of the Heterogeneous Catalyst to Produce Solketal from Biodiesel Waste: The Key to Achieve Efficiency.

The valorization of the large amount of crude glycerol formed from the biodiesel industry is of primordial necessity. One possible direction with high interest to the biorefinery sector is the production of fuel additives such as solketal, through the acetalization of glycerol with acetone. This is a chemical process that conciliates high sustainability and economic interest, since solketal contributes to the fulfillment of a Circular Economy Model through its use in biodiesel blends. The key to guarantee high efficiency and high sustainability for solketal production is the use of recovery and recyclable heterogeneous catalysts. Reported works indicate that high yields are attributed to catalyst acidity, mainly the ones containing Brönsted acidic sites. On the other hand, the catalyst stability and its recycling capacity are completely dependent of the support material and the acidic sites incorporation methodology. This review intends to conciliate the information spread on this topic and indicate the most assertive strategies to achieve high solketal production in short reaction time during various reaction cycles.

The ASSIST trial: Acute effects of manipulating strength exercise volume on insulin sensitivity in obese adults: A protocol for a randomized controlled, crossover, clinical trial.

Type 2 diabetes mellitus is a disease in which insulin action is impaired, and an acute bout of strength exercise can improve insulin sensitivity. Current guidelines for strength exercise prescription suggest that 8 to 30 sets could be performed, although it is not known how variations in exercise volume impact insulin sensitivity. Additionally, this means an almost 4-fold difference in time commitment, which might directly impact an individual's motivation and perceived capacity to exercise. This study will assess the acute effects of high- and low-volume strength exercise sessions on insulin sensitivity. After being thoroughly familiarized, 14 obese individuals of both sexes (>40 year old) will undergo 3 random experimental sessions, with a minimum 4-day washout period between them: a high-volume session (7 exercises, 3 sets per exercise, 21 total sets); a low-volume session (7 exercises, 1 set per exercise, 7 total sets); and a control session, where no exercise will be performed. Psychological assessments (feeling, enjoyment, and self-efficacy) will be performed after the sessions. All sessions will be held at night, and the next morning, an oral glucose tolerance test will be performed in a local laboratory, from which indexes of insulin sensitivity will be derived. We believe this study will aid in strength exercise prescription for individuals who claim not to have time to exercise or who perceive high-volume strength exercise intimidating to adhere to. This trial was prospectively registered (ReBEC #RBR-3vj5dc5 https://ensaiosclinicos.gov.br/rg/RBR-3vj5dc5).

Fabrication and characterization of physically crosslinked alginate/chitosan-based hydrogel loaded with neomycin for the treatment of skin infections caused by Staphylococcus aureus.

Staphylococcus aureus is a pathogen widely involved in wound infection due to its ability to release several virulence factors that impair the skin healing process, as well as its mechanism of drug resistance. Herein, sodium alginate and chitosan were combined to produce a hydrogel for topical delivery of neomycin to combat S. aureus associated with skin complications. The hydrogel was formulated by combining sodium alginate (50 mg/mL) and chitosan (50 mg/mL) solutions in a ratio of 9:1 (HBase). Neomycin was added to HBase to achieve a concentration of 0.4 mg/mL (HNeo). The incorporation of neomycin into the product was confirmed by scanning electron microscopy, FTIR and TGA analysis. The hydrogels produced are homogeneous, have a high swelling capacity, and show biocompatibility using erythrocytes and fibroblasts as models. The formulations showed physicochemical and pharmacological stability for 60 days at 4 ± 2 °C. HNeo totally inhibited the growth of S. aureus after 4 h. The antimicrobial effects were confirmed using ex vivo (porcine skin) and in vivo (murine) wound infection models. Furthermore, the HNeo-treated mice showed lower severity scores than those treated with HBase. Taken together, the obtained results present a new low-cost bioproduct with promising applications in treating infected wounds.

The Effect of Phenolic-Rich Extracts of Rubus fruticosus, R. ulmifolius and Morus nigra on Oxidative Stress and Caco-2 Inhibition Growth.

Currently, a clear interest has been given to berries due to their richness in active metabolites, including anthocyanins and non-coloured phenolics. Therefore, the main aim of the present work is to investigate the phenolic profile, antioxidant abilities, and antiproliferative effects on normal human dermal fibroblasts (NHDF) and human colon carcinoma cell line (Caco-2) cells of phenolic-rich extracts from three red fruits highly appreciated by consumers: two species of blackberries (Rubus fruticosus and Rubus ulmifolius) and one species of mulberry (Morus nigra). A total of 19 different phenolics were identified and quantified by HPLC-DAD-ESI/MSn and HPLC-DAD, respectively. Focusing on the biological potential of the phenolic-rich extracts, all of them revealed notable scavenging abilities. Concerning the antiproliferative properties, R. fruticosus presented a cytotoxic selectivity for Caco-2 cells compared to NHDF cells. To deeper explore the biological potential, combinations with positive controls (ascorbic acid and 5-fluorouracil) were also conducted. Finally, the obtained data are another piece of evidence that the combination of phenolic-rich extracts from natural plants with positive controls may reduce clinical therapy costs and the possible toxicity of chemical drugs.

Prophylactic use of standardized extract of propolis of Apis mellifera (EPP-AF®) reduces lung inflammation and improves survival in experimental lethal sepsis.

ETHNOPHARMACOLOGICAL RELEVANCE: Sepsis poses one of the biggest public health problems, necessitating the search for new therapeutic alternatives. For centuries, propolis has been widely used in folk medicine to treat various inflammatory and infectious diseases. Given its extensive use, it has excellent potential as an adjuvant treatment for patients with sepsis. OBJECTIVE: This study evaluated prophylactic treatment with standardized propolis extract (EPP-AF®) and followed the prognosis of sepsis induced by ligation and cecal ligation and puncture (CLP). METHODS: Initially, for survival assessment, Swiss mice were separated into five groups: Sham (false operated), control (PBS), ATB (received antibiotic, 8 mg/kg), P10 (received EPP-AF®, 10 mg/kg), and P100 (received EPP-AF®, 100 mg/kg). The animals received PBS, antibiotic, or EPP-AF® by the subcutaneous route 6 h before the CLP procedure. Animal survival was assessed every 12 h for five days when all of them were euthanized. RESULTS: We show that the treatment with EPP-AF® significantly increased the life expectancy of animals with sepsis compared to the control group. Interestingly, prophylactic treatment with EPP-AF® showed no effect on the number of colony-forming units in the peritoneum, blood, or lung. However, there was a decrease in cellular influx in the peritoneum. This alteration was unrelated to the number of bone marrow cells or the differential counting of peripheral blood cells. The coagulogram remained unchanged, including the number of platelets and prothrombin time-activated partial thromboplastin time. However, the inflammatory infiltrate and bleeding in the lung tissue were lower in the animals that received EPP-AF®. CONCLUSION: Thus, it was possible to conclude that prophylactic treatment with EPP-AF® preserved the lung parenchyma, resulting in an increased lifespan of mice with sepsis. It can be a helpful adjuvant in prophylactic treatment with antibiotics in presurgical conditions.

Advanced technologies in water treatment: Chitosan and its modifications as effective agents in the adsorption of contaminants.

Chitosan, derived from the abundant biopolymer chitin, has emerged as a promising option for water treatment due to its intrinsic bioavailability. This review emphasizes the notable characteristics of chitosan, which allow for various modifications, expanding its applications. The polymer's effectiveness in adsorbing contaminants, particularly in advanced water treatment technologies, is highlighted. The review underscores the potential of chitosan-based hybrid materials, including nanocomposites, hydrogels, membranes, films, sponges, nanoparticles, microspheres, and flakes, as innovative alternatives to traditional chemical-based adsorbents. The advantages of using these materials in wastewater treatment, especially in removing heavy metals, dyes, and emerging compounds, are explored. The study delves into the mechanisms involved in wastewater treatment with chitosan, emphasizing the interactions between the polymer and various contaminants. Additionally, the application of chitosan as a contaminant removal agent in a post-pandemic context is addressed, considering the challenges related to waste management and environmental preservation. The analysis highlights the potential contribution of chitosan in mitigating environmental impacts post-pandemic, offering practical solutions for treating contaminated effluents and promoting sustainability. The study addresses current obstacles and prospects for chitosan-based wastewater treatment, emphasizing its promising role in sustainable water management.

Potential Role of Dietary Phenolic Compounds in the Prevention and Treatment of Rheumatoid Arthritis: Current Reports.

Rheumatoid arthritis (RA) is a complex illness with both hereditary and environmental components. Globally, in 2019, 18 million people had RA. RA is characterized by persistent inflammation of the synovial membrane that lines the joints, cartilage loss, and bone erosion. Phenolic molecules are the most prevalent secondary metabolites in plants, with a diverse spectrum of biological actions that benefit functional meals and nutraceuticals. These compounds have received a lot of attention recently because they have antioxidant, anti-inflammatory, immunomodulatory, and anti-rheumatoid activity by modulating tumor necrosis factor, mitogen-activated protein kinase, nuclear factor kappa-light-chain-enhancer of activated B cells, and c-Jun N-terminal kinases, as well as other preventative properties. This article discusses dietary polyphenols, their pharmacological properties, and innovative delivery technologies for the treatment of RA, with a focus on their possible biological activities. Nonetheless, commercialization of polyphenols may be achievable only after confirming their safety profile and completing successful clinical trials.

Effects of Smallanthus sonchifolius Flour on Metabolic Parameters: A Systematic Review.

Smallanthus sonchifolius, popularly known as yacon, is a member of the Asteraceae family. Due to its medicinal and edible value, yacon is consumed by different populations. Yacon is unique due to its high fructo-oligosaccharide and inulin content, as well as flavonoids, sesquiterpene lactones, and phenolic acids. Roots can be used to produce flour, which is less perishable and can be applied in various industrial products. This systematic review focuses on the effects of yacon flour on metabolic parameters. PubMed, Cochrane, Embase, Science Direct, Scopus, Web of Science, and Google Scholar databases were consulted, and PRISMA guidelines were followed in the selection of the studies. In total, 526 articles were found in the databases, and of these, only 28 full texts were eligible for inclusion. After applying the inclusion and exclusion criteria, seven studies were finally included. The results showed that the use of yacon flour can reduce glycemia, HbA1c, advanced glycation ends, plasma lipids, body fat mass, body weight, and waist circumference and improve intestinal microbiota and the antioxidant status. Further exploration of the effects of yacon flour is warranted, and additional clinical trials are necessary to determine the optimal daily consumption levels required to assist in improving metabolic parameters.

Antioxidant activity of the main phenolics found in red fruits: An in vitro and in silico study.

The current study analysed the antioxidant capacity of the main phenolics found in red fruits. In total, there were analysed the antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl radical, nitric oxide and superoxide radicals (DPPH, NO and O2-, respectively) of 23 phenolics. Regarding DPPH, anthocyanins, (-)-epicatechin and kaempferol 3-O-rutinoside were the most active, while isorhamnetin 3-O-glucoside was the least active. Anthocyanins, (-)-epicatechin, quercetin 3-O-glucoside and caffeic acid showed the strongest potential against NO, while ρ-hydroxybenzoic acid was the less efficient. Regarding the O2- assay, quercetin aglycone and their derivatives were the best ones, while cyanidin aglycone did not show any potential to quench this radical. To deeper explore the biological potential of the most promising compounds, docking molecular and ADME studies were also done. The obtained data is another support regarding the biological potential of phenolics and might be useful in encouraging their use and incorporation in new products.

Evaluation of Microbiological Susceptibility and Long-term Adhesive Properties to Dentin of Primers with Terminalia catappa Linn.

PURPOSE: To investigate the antibacterial effects of Terminalia catappa Linn (TCL) leaf extracts at different concentrations and the effects of these extracts used as primers on the long-term adhesive properties of two universal adhesives. MATERIALS AND METHODS: After extract preparation, the antimicrobial and antibacterial activities of TCL against Streptococcus mutans (UA 159) were assessed in microdilution assays to provide the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). Additionally, to provide quantitative data on the ability of TCL extract to reduce cell viability, colony forming units (CFU) were counted. To examine adhesive properties, 288 human molars were randomly assigned to 32 experimental conditions (n = 9) according to the following variables: (1) treatment agent: negative control (untreated surface), and primers at concentrations of 1xMIC, 5xMIC, and 10xMIC; (2) adhesives: Scotchbond Universal (SBU) and Futurabond Universal (FBU); (3) adhesive strategy: etch-and-rinse (ER) or self-etch (SE); and (4) storage time: 24 h or after 2 years. Primers were applied for 60 s, upon which the teeth were incrementally restored and sectioned into adhesive-dentin bonded sticks. These were tested for microtensile bond strength (µTBS) and nanoleakage (NL) after 24-h and 2-year water storage, as well as in-situ degree of conversion (DC) at 24 h. The chemical profile of the hybrid layer was determined via micro-Raman spectroscopy. Biofilm assay data were analyzed using the Kruskal-Wallis test; the pH of culture media and the chemical profile were analyzed by one-way ANOVA. The adhesive properties (µTBS, NL, DC) were evaluated using a four-way ANOVA and Tukey's test. Significance was set at 5%. RESULTS: Similar values of MIC and MBC were observed (2 mg/ml), showing bactericidal potential. CFU analysis demonstrated that concentrations of 5xMIC and 10xMIC significantly inhibited biofilm formation (p < 0.001). The application of the TCL primer at all concentrations significantly increased the immediate µTBS and DC, and decreased the immediate NL values when compared to the control group (p < 0.05), regardless of the adhesive and adhesive strategies. Despite an increase in the NL values for all groups after 2 years (p > 0.05), in groups where the TCL primer was applied, the µTBS remained constant after 2 years for both adhesives, while a decrease in the µTBS was observed in the control groups (p < 0.05). Usually, 10xMIC showed better results than 1xMIC and 5xMIC (p < 0.05). The application of TCL promoted cross-linking; cross-linking rates increased proportionally to the concentration of TCL (p < 0.05). CONCLUSION: Primers containing TCL promoted bactericidal and bacteriostatic action, as well as cross-linking with dentin, while maintaining the adhesive properties of the adhesive-dentin interface after 2 years of water storage.

Porous Coordination Polymer MOF-808 as an Effective Catalyst to Enhance Sustainable Chemical Processes.

The improvement of sustainable chemical processes plays a pivotal role in safe environmental and societal development, for example, by reducing the use of hazardous substances, preventing chemical waste, and improving the efficiency of chemical reactions to obtain added-value compounds. In this context, the porous coordination polymer MOF-808 (MOF, metal-organic framework) was prepared by a straightforward method in water, at room temperature, and was unequivocally characterized by powder X-ray diffraction, vibrational spectroscopy, thermogravimetric analysis, and scanning electron microscopy. MOF-808 material was applied for the first time as catalysts in ring-opening aminolysis reactions of epoxides. It demonstrated high activity and selectivity for reactions of styrene oxide and cyclohexene oxide with aniline, using a very low amount of an eco-sustainable solvent (0.5 mL of EtOH), at 70 °C. Moreover, MOF-808 demonstrated high stability in the catalytic reaction conditions applied, and a notable reuse capacity of up to 20 consecutive reaction cycles, without significant variation in its catalytic performance. In fact, this Zr-based porous coordination polymer prepared by environment-friendly conditions proved to be a novel efficient heterogeneous catalyst, promoting the ring-opening reaction of epoxides under more sustainable conditions, and using a very low amount of catalyst.

Research Trends in Proteomic Studies Using Serum from COVID-19 Patients: A Bibliometric Analysis.

The COVID-19 pandemic significantly impacted the global populace, resulting in a staggering number of deaths across the globe. New approaches and biomarkers to evaluate disease progression are crucial for improving disease management. In this context, serum proteomics has emerged as a promising tool for identifying molecular alterations related to COVID-19. This work carried out a bibliometric evaluation of the current status and trends of studies applying serum proteomics to COVID-19 subjects. The search was performed using Web of Science and Scopus databases, and the results were analyzed in VOSviewer software. The investigation was limited to articles published between January 2020 and February 2023. The analysis found 48 articles, primarily experimental studies. China is the most influential country in this field, followed by the USA. The co-occurrence analysis performed by VOSviewer showed 170 keywords, of which 9 reached the occurrence threshold and were divided into two groups. The most cited words were related to biomarker identification and the use of proteomics for diagnosing and treating COVID-19. The most cited proteins include those classically associated with the immune system (IgG, IgM, interleukins, CXCL, CCL, MCP, CRP) and SAA1, SAA1, ApoA-1, TTR (prealbumin), SerpinA and ITIH4. Other studies have validated the predictive value of these serum markers and have the potential to improve the management of COVID-19 patients. The findings highlighted in this bibliometric study can help the researchers design new projects to enhance our understanding of the complex interplay between SARS-CoV-2 and host immunity.

Real-World Evidence of the Long-Term Effectiveness of 0.2 µg/Day Fluocinolone Acetonide Implant in Persistent and Recurrent Diabetic Macular Edema - A Single Center Study.

Purpose: To report the long-term functional, anatomical and safety outcomes of 0.2 µg/day fluocinolone acetonide 0.19mg in patients with persistent or recurrent diabetic macular edema (DME). Methods: Retrospective, observational, single-center study of patients with recurrent or persistent DME. All patients received 0.2 µg/day of fluocinolone acetonide 0.19mg, and data were collected at baseline and months 1, 3, 6, 12, 24 and 36 after implantation. Outcomes measured included best-corrected visual acuity (BCVA), central macular thickness (CMT), intraocular pressure (IOP), and safety outcomes. Results: A total of 28 eyes from 28 patients were included. The mean age was 66.5 years (95% CI 62.8-70.2) with a mean duration of DME of 8.8 years (95% CI 7.7-10.0). Only two eyes were phakic. Mean follow-up was 25.4 months (95% CI 21.2-29.6). Mean BCVA at baseline was 48.6 ETDRS letters (95% CI 41.3-55.8) and improved as early as month 1 of follow-up with a mean gain in BCVA of 7.8 (95% CI 4.3-11.3) ETDRS letters (p<0.001). Statistically significant improvements in BCVA were also observed at months 6, 12 and 24. At baseline, patients had a mean CMT of 530.5µm (95% CI 463.0-598.0), and a decrease in CMT was observed, starting at the first month of follow-up (mean CMT reduction of -170.5µm, 95% CI -223.8- -117.1; p<0.001). Statistically significant decreases in CMT were also observed at months 6, 12, 24, and 36, with the maximum decrease observed at month 12 (p<0.001). Mean IOP at baseline was 16.4mmHg (95% CI 15.3-17.5) and nine eyes (32.1%) had an IOP ≥21mmHg during follow-up. Conclusion: Our results support the effectiveness and safety profile of fluocinolone acetonide. Although additional long-term real-world evidence is required, fluocinolone acetonide may represent a safe strategy for daily, low-dose, sustained and localized release to the posterior segment of the eye, providing both functional and anatomical benefits in DME.

New avenues for the treatment of immunotherapy-resistant pancreatic cancer.

Pancreatic cancer (PC) is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide. However, due to its complexity, it ranks 7th in the list of the most lethal cancers worldwide. The pathogenesis of PC involves several complex processes, including familial genetic factors associated with risk factors such as obesity, diabetes mellitus, chronic pancreatitis, and smoking. Mutations in genes such as KRAS, TP53, and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and, consequently, cancer. In this context, some therapies are used for PC, one of which is immunotherapy, which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy efficiency. It is therefore clear that the tumor microenvironment (TME) has a huge impact on the resistance process, since cellular and non-cellular elements create an immunosuppressive environment, characterized by a dense desmoplastic stroma with cancer-associated fibroblasts, pancreatic stellate cells, extracellular matrix, and immunosuppressive cells. Linked to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells, resulting in a shortage of CD8+ T cells and limited expression of activation markers such as interferon-gamma. In this way, finding new strategies that make it possible to manipulate resistance mechanisms is necessary. Thus, techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance, the use of genetic manipulation in specific regions, such as microRNAs, the modulation of extrinsic and intrinsic factors associated with T cells, and, above all, therapeutic models that combine these modulation techniques constitute the promising future of PC therapy. Thus, this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating this process, resulting in a more efficient therapy for cancer patients and, consequently, a reduction in the lethality of this aggressive cancer.

Gross, organoleptic and histologic assessment of cadaveric equine heads preserved using chemical methods for veterinary surgical teaching.

BACKGROUND: Preservation of biological tissues has been used since ancient times. Regardless of the method employed, tissue preservation is thought to be a vital step in veterinary surgery teaching and learning. OBJECTIVES: This study was designed to determine the usability of chemically preserved cadaveric equine heads for surgical teaching in veterinary medicine. METHODS: Six cadaveric equine heads were collected immediately after death or euthanasia and frozen until fixation. Fixation was achieved by using a hypertonic solution consisting of sodium chloride, sodium nitrite and sodium nitrate, and an alcoholic solution containing ethanol and glycerin. Chemically preserved specimens were stored at low temperatures (2°C to 6°C) in a conventional refrigerator. The specimens were submitted to gross and organoleptic assessment right after fixative solution injection (D0) and within 10, 20, and 30 days of fixation (D10, D20, and D30, respectively). Samples of tissue from skin, tongue, oral vestibule, and masseter muscle were collected for histological evaluation at the same time points. RESULTS: Physical and organoleptic assessments revealed excellent specimen quality (mean scores higher than 4 on a 5-point scale) in most cases. In some specimens, lower scores (3) were assigned to the range of mouth opening, particularly on D0 and D10. A reduced the range of mouth opening may be a limiting factor in teaching activities involving structures located in the oral cavity. CONCLUSIONS: The excellent physical, histologic, and organoleptic characteristics of the specimens in this sample support their usability in teaching within the time frame considered. Appropriate physical and organoleptic characteristics (color, texture, odor, and flexibility) of the specimens in this study support the use of the method described for preparation of reusable anatomical specimens.