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Background/Objectives: Head and neck cancer (HNC) is the sixth most common cancer worldwide, with a high mortality, particularly from head and neck squamous cell carcinoma (HNSCC). Although some therapeutic strategies are available, they might cause severe side effects. For example, surgery may result in disfigurement and functional loss, severely impacting the patient’s quality of life. Thus, minimally invasive and more effective alternatives are needed. Gold nanoparticle (AuNP)-mediated photothermal therapy (PTT) is a promising approach for HNC, which relies on AuNP photothermal efficiency and tumor localization. This study aimed to synthesize and characterize AuNPs, evaluate their safety without laser activation, and assess their efficacy with laser activation. Methods and Results: Their physicochemical and photostability over three months and sterility were confirmed. In vitro safety was tested using human non-cancerous and HNC cell lines, while in vivo biocompatibility was evaluated in the hen’s egg chorioallantoic membrane (CAM) model, with no adverse effects observed. Upon laser activation, AuNPs reduced HNC cell viability by 50–70%, including HNSCC lines. In vivo biodistribution studies showed that AuNPs remained at the injection site for up to one month without toxicity. Conclusions: Overall, the developed AuNP formulation demonstrates stability, biocompatibility, and prolonged local retention, key attributes for effective and targeted PTT. These findings support the potential of AuNP-mediated photothermal therapy as a promising treatment modality for HNC, although further preclinical and clinical studies are needed to optimize treatment parameters.

We report the synthesis and characterization of five novel metal complexes. Three of them are vanadium complexes with the general formula [VO(Ln)2], where Ln are Schiff bases derived from the condensation of 2-carbaldehyde-8-hydroxyquinoline with either 4-(2-aminoethyl)morpholine (L1), 3-morpholinopropylamine (L2) or 1-(2-aminoethyl)piperidine (L3). The two other metal complexes are [Ni(L1)2] and [Fe(L1)2]Cl. They were characterized by analytical, spectroscopic (Fourier transform infrared, UV-visible absorption), and mass spectrometric techniques as well as by single-crystal X-ray diffraction (for all [VO(Ln)2] complexes and [Ni(L1)2]). While, in the crystal structure, the V(IV)O complexes show distorted square–pyramidal geometry with the ligands bound as bidentate through quinolate NO donors, the Ni(II) complex shows octahedral geometry with two ligand molecules coordinated through NNO donors. Stability studies in aqueous media revealed that the vanadium complexes are not stable, undergoing oxidation to VO2(L), which was corroborated by 51V NMR and MS. This behavior is also observed in organic media, though at a significantly slower rate. The Ni complex exhibited small spectral changes over time in aqueous media. Nonetheless, all compounds show enhanced stability in the presence of bovine serum albumin (BSA). Fluorescence studies carried out for the Ni(II) and Fe(III) complexes indicate reversible binding to albumin. The cytotoxicity of the L1 metal complexes was assessed on melanoma (B16F10 and A375) and colon cancer (CT-26 and HCT-116) cell lines, with 5-fluorouracil (5-FU) as a reference drug. The V- and Ni complexes showed the lowest IC50 values (<10 μM) in either A375 or HCT-116 cells after 48 h of incubation, while the Fe(III) complex presented minimal antiproliferative effects. The complexes were generally more cytotoxic to human than murine cancer cells. Synergistic in vitro studies with 5-FU revealed antagonism in most cases, except in A375 cells, where an additive effect was observed for the combination with the V-complex. Overall, these compounds show promising potential for cancer treatment, mostly for melanoma.

Colorectal cancer (CRC) is the third most prevalent malignancy worldwide and in both sexes. Numerous animal models for CRC have been established to study its biology, namely carcinogen-induced models (CIMs) and genetically engineered mouse models (GEMMs). CIMs are valuable for assessing colitis-related carcinogenesis and studying chemoprevention. On the other hand, CRC GEMMs have proven to be useful for evaluating the tumor microenvironment and systemic immune responses, which have contributed to the discovery of novel therapeutic approaches. Although metastatic disease can be induced by orthotopic injection of CRC cell lines, the resulting models are not representative of the full genetic diversity of the disease due to the limited number of cell lines suitable for this purpose. On the other hand, patient-derived xenografts (PDX) are the most reliable for preclinical drug development due to their ability to retain pathological and molecular characteristics. In this review, the authors discuss the various murine CRC models with a focus on their clinical relevance, benefits, and drawbacks. From all models discussed, murine CRC models will continue to be an important tool in advancing our understanding and treatment of this disease, but additional research is required to find a model that can correctly reflect the pathophysiology of CRC.

The antimicrobial activity of dehydroabietic acid (DHA) for its use as an antibiofilm agent was tested in this work. DHA was assayed against a collection of Gram-positive, Gram-negative sensitive and resistant bacteria and yeasts through the minimum inhibitory concentration (MIC), MIC with Bioburden challenge, minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC), MBIC with Bioburden challenge and growth curve studies. Toxicological studies (Artemia salina, sulforhodamine B (SRB) assay) were done to assess if the compound had antimicrobial and not cytotoxic properties. Furthermore, microencapsulation and stability studies were carried out to evaluate the chemical behavior and stability of DHA. On MIC results, Gram-positive bacteria Staphylococcus aureus ATCC 1228 and Mycobacterium smegmatis ATCC 607 presented a high efficiency (7.81 µg/mL), while on Gram-negative bacteria the highest MIC value of 125 µg/mL was obtained by all Klebsiella pneumoniae strains and Escherichia coli isolate strain HSM 303. Bioburden challenge showed that MIC, MBIC and percentage biofilm inhibition (BI) values suffered alterations, therefore, having higher concentrations. MBIC values demonstrated that DHA has a higher efficiency against S. aureus ATCC 43866 with a percentage of BI of 75.13 ± 0.82% at 0.49 µg/mL. Growth curve kinetic profiles of DHA against S. aureus ATCC 25923 were observed to be bacteriostatic. DHA-alginate beads had a average size of 2.37 ± 0.20 and 2.31 ± 0.17 × 103 µm2 with an encapsulation efficiency (EE%) around 99.49 ± 0.05%, a protection percentage (PP%) of 60.00 ± 0.05% in the gastric environment and a protection efficiency (PE%) around 88.12 ± 0.05% against UV light. In toxicological studies DHA has shown IC50 of 19.59 ± 7.40 µg/mL and a LC50 of 21.71 ± 2.18%. The obtained results indicate that DHA is a promising antimicrobial candidate against a wide range of bacteria and biofilm formation that must be further explored.

We report the synthesis and characterization of five novel metal complexes. Three of them are vanadium complexes with the general formula [VO(Ln)2], where L[sup.n] are Schiff bases derived from the condensation of 2-carbaldehyde-8-hydroxyquinoline with either 4-(2-aminoethyl)morpholine (L[sup.1]), 3-morpholinopropylamine (L[sup.2]) or 1-(2-aminoethyl)piperidine (L[sup.3]). The two other metal complexes are [Ni(L1)2] and [Fe(L1)2]Cl. They were characterized by analytical, spectroscopic (Fourier transform infrared, UV-visible absorption), and mass spectrometric techniques as well as by single-crystal X-ray diffraction (for all [VO(Ln)2] complexes and [Ni(L1)2]). While, in the crystal structure, the V(IV)O complexes show distorted square–pyramidal geometry with the ligands bound as bidentate through quinolate NO donors, the Ni(II) complex shows octahedral geometry with two ligand molecules coordinated through NNO donors. Stability studies in aqueous media revealed that the vanadium complexes are not stable, undergoing oxidation to VO[sub.2](L), which was corroborated by [sup.51]V NMR and MS. This behavior is also observed in organic media, though at a significantly slower rate. The Ni complex exhibited small spectral changes over time in aqueous media. Nonetheless, all compounds show enhanced stability in the presence of bovine serum albumin (BSA). Fluorescence studies carried out for the Ni(II) and Fe(III) complexes indicate reversible binding to albumin. The cytotoxicity of the L[sup.1] metal complexes was assessed on melanoma (B16F10 and A375) and colon cancer (CT-26 and HCT-116) cell lines, with 5-fluorouracil (5-FU) as a reference drug. The V- and Ni complexes showed the lowest IC[sub.50] values (<10 μM) in either A375 or HCT-116 cells after 48 h of incubation, while the Fe(III) complex presented minimal antiproliferative effects. The complexes were generally more cytotoxic to human than murine cancer cells. Synergistic in vitro studies with 5-FU revealed antagonism in most cases, except in A375 cells, where an additive effect was observed for the combination with the V-complex. Overall, these compounds show promising potential for cancer treatment, mostly for melanoma.

This dissertation focused on the development of novel abietane cationic amphiphiles (ACAs) by chemical modification of dehydroabietic acid (DHA), leading to cationic amide derivatives by condensation of the DHA carboxyl function with the amine group of biogenic polyamines (spermine) and basic proteinogenic amino acids (arginine). After ACAs several synthesis procedures were performed, and subsequently TLC and NMR analyses, it was concluded that no molecular form was identified in the form of an amide, but rather the intermediary product and products of degradation.The presented dissertation performed a screening of antimicrobial activities of the compounds DHA and ACA hemi-synthesis intermediary (ACA-Int) against a collection of Gram-positive, Gram-negative bacteria and yeasts; toxicological studies to assess if the compounds had antimicrobial and not citotoxic properties; and microencapsulation and stability studies to evaluate the chemical behavior and stability of the tested compounds.The antimicrobial activity screening of DHA and ACA-Int showed that both compounds had inhibited the planktonic and biofilm growth of a collection of Gram-positive and Gram-negative bacteria and a yeast.In addition, the MIC, MIC with organic interfering substances , MBC, MBIC, MBIC with organic interfering substances and time-kill kinetic study against standard and clinical isolates of sensitive and resistant bacterial strains was determined for DHA and ACA-Int.In MICs studies DHA demonstrated to have higher efficacy than the ACA-Int in Gram-positive bacteria S. epidermidis ATCC 12228 and M. smegmatis ATCC 607 both with the lowest MIC value (7.81 μg/mL); and in Gram-negative bacteria, all clinical isolates of K. pneumoniae and clinical isolate strain E. coli3023 with a MIC value of 125.00 μg/mL. The studies of MIC with organic interfering substances have showed that organic challenges have influence in MIC values thus increasing them.Regarding to MBC values, the results showed low MBC/MIC ratios within each strain, which is typical for bactericidal agents.In biofilm formation assay, most of the tested microorganisms were biofilm producer except for clinical isolate Ent. Cloacae 1264. Concerning the biofilm inhibition properties of DHA and ACA-Int, where the lowest MBICs value registered of DHA was achieved against Gram-positive S aureus ATCC 43866 (0.49 μg/mL; BI = 75.13±8.82%) which is a strong biofilm producer. In Gram-negative bacteria, the lowest MBIC was showed against clinical isolates K. pneumoniae 701 (0.98 μg/mL; BI = 92.75±5.69%) and K. pneumoniae 703 (0.98 μg/mL; BI = 94.13±2.37%). DHA and ACA-Int were also tested against C. albicansATCC 10231 and they achieved MBIC values of 62.50 μg/mL; BI = 81.83±7.05% and 125.00 μg/mL; BI = 57.85±24.64%, respectively.With MBIC organic interfering substances, in Gram-positive bacteria only HBS has more influence in MBIC and BI, yet in Gram-negative bacteria all challenges had influence in MBIC and BI values.Time-kill kinetics profiles of DHA against the test organisms (S. aureusATCC 25923) at concentrations of 31.25, 62.50 and 93.75 μg/mL showed that this compound has bacteriostatic properties. Nonetheless, as a future perspective regarding antimicrobial assays, it would be important to better understand the mechanisms of action of these diterpenes.Regarding to the microencapsulation of the compounds, it was achieved a EE% of 99.49±0.05%, and the stability studies demonstrated that DHA remains stable within alginate beads (PP% = 60.00±0.05%; PE% = 88.12±0.05%).

This dissertation assessed the existence of a gap between the brand image and brand identity for CAIS, a Portuguese non-profit organization known for its emblematic product: CAIS magazine and the recommendation of corrective strategic actions that might be undertaken by CAIS to narrow the gap. Therefore, CAIS identity was inferred through interviews and research about the organization, as well as, CAIS brand image measurement through a survey which asked respondents to rate attributes related to the statute, size, geographic coverage, vision, mission, objectives, core competencies, personality, beneficiaries and relationship on a 7-point scale according to the extent of which the respondent feels the brand CAIS is associated to a certain attribute. Based on both data collected regarding the organization’s identity and image, the gap between the two concepts was identified and evaluated though the measurement of the difference between 7 or 1, depending if the attribute was related or not with CAIS identity and the median of the results obtained through the survey. The findings suggest that a gap between image and identity exist regarding CAIS vision, mission, core competencies and beneficiaries. The gap assessment allowed to conclude that CAIS brand image is linked in great extent to CAIS magazine. There is a lack of knowledge regarding CAIS as an organization beyond the magazine and the image people hold about CAIS corresponds to CAIS identity at the time of its foundation in 1994. Therefore, CAIS might undertake some suggested corrective strategic actions in order to reduce the observed gap like: development of a national campaign to increase general public awareness about CAIS, increase of brand communication through media, expand CAIS micro businesses and implement measures that guarantee CAIS magazine sellers compliance with the code of conduct.

This study evaluated the impact of yellow mombin (Spondias mombin L.) bagasse extract (YMBE) on the color degradation, protein and lipid oxidation in ready-to-eat chicken patties during 15 days of refrigerated storage. Two formulations of chicken patties were developed: chicken patties control - PCON (without the antioxidant extract) and chicken patties with yellow mombin extract - PYME (with the antioxidant extract). The extract was effective in maintaining red color and inhibiting myoglobin degradation in the evaluated samples. The generation of lipid oxidation compounds during storage of the treated samples was delayed by 92.37% for peroxide index, 89.89% for conjugated dienes, 74.29% for tiobarbituric acid reactive substances (TBARs) and 92.55% for ρ-anisidine compared to the control samples. Moreover, the addition of YMBE inhibited the formation of carbonyl compounds during cold storage compared to the control samples. Extracts obtained from the yellow mombin bagasse act as a good natural antioxidant for ready-to-eat chicken patties inhibiting protein and lipid oxidative damage during cold storage, being a potential preservative to replace synthetic antioxidants in meat products.

Fatigue is a frequent complaint in kidney transplant recipients (KTR), often accompanied by poor quality of life (QoL). The role of nutrition as determinant of fatigue in KTR is largely unexplored. The aims of this study are to examine the association of protein intake with fatigue and QoL in KTR and to identify other determinants of fatigue. This cross-sectional study is part of the TransplantLines Cohort and Biobank Study (NCT03272841). Protein intake was calculated from urinary urea nitrogen (UUN) in 24-h urine samples. Fatigue was assessed by the Checklist Individual Strength (CIS) questionnaire; moderate and severe fatigue were defined as a CIS score of 20–34 and ≥ 35, respectively. QoL was assessed with the RAND-36-Item Health Survey (RAND-36). Associations of protein intake with fatigue and QoL were analyzed using multinomial logistic and linear regression analyses. We included 730 stable outpatient KTR (median age 58 year [IQR 48–65], 57% male) with a mean protein intake of 82.2 ± 21.3 g/d. Moderate and severe fatigue were present in 254 (35%) and 245 (34%) of KTR. Higher protein intake was significantly associated with lower risk of moderate fatigue (OR 0.89 per 10 g/d; 95%CI 0.83–0.98, p = 0.01), severe fatigue (OR 0.85; 95%CI 0.78–0.92, p < 0.001) and was associated with higher physical component summary score of QoL (β 0.74 per 10 g/d; 95%CI 0.39–1.09, p < 0.001). Higher BMI, a history of dialysis, glomerulonephritis as primary kidney disease and a history of combined organ transplantation were also associated with severe fatigue. In conclusion, amongst the potential modifiable factors of fatigue, higher protein intake is independently associated with lower risk of moderate and severe fatigue and with better QoL in KTR. These findings underline the need to incorporate nutritional assessment in the diagnostic work-up of fatigue. Intervention studies are needed to assess the benefits and safety of higher protein intake in KTR.

•More than one-third (36%) of patients are malnourished before discharge from hospital.•Prevalence of malnutrition is higher in patients with a longer length of stay.•Approximately 30% of well-nourished patients at admission are malnourished predischarge.•Follow-up of nutritional status and adequate transmural nutritional care are recommended. In Dutch hospitals malnutrition screening is routinely performed at admission, but not during follow-up or before discharge. Therefore we evaluated nutritional status during hospitalization and predischarge in a routine care setting. The Patient-Generated Subjective Global Assessment (PG-SGA) was used to assess nutritional status (PG-SGA Categories: A = well nourished, B = moderate/suspected malnutrition, C = severely malnourished) in adult patients on four wards of a university hospital at admission, day 5, day 10, and day ≥15. Because data were obtained in the context of clinical routine, not all data points are available for all patients. Last assessment before discharge (within ≤4 d) was taken as predischarge measurement. PG-SGA data at admission were obtained in 584 patients (age 57.2 ± 17.3 y, 51.4% women, body mass index 27.0 ± 5.5 kg/m2). Prevalence of PG-SGA stage B/C was 31% at admission, 56% on day 5 (n = 292), 66% on day 10 (n = 101), and 79% on day ≥15 (n = 14). PG-SGA predischarge data were available in 537 patients, 36% of whom were PG-SGA stage B/C. Of the 91 patients assessed both at admission and predischarge, 30% of well-nourished patients became malnourished and 82% of malnourished patients remained so. Prevalence of malnutrition in hospitalized patients is high at admission (31%) and, importantly, also high predischarge (36%). Malnutrition is more prevalent in patients with a longer length of stay. These findings underscore the importance of follow-up of nutritional status in hospitalized patients and adequate transmural nutrition care after discharge to prevent malnutrition from remaining undetected and untreated.