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1.
Proc Natl Acad Sci U S A ; 121(33): e2407357121, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39110724

RESUMEN

Satellite-based land use monitoring and farm-level traceability offer opportunities for targeted zero-deforestation interventions on private lands. Brazil's Rural Environmental Registry (Cadastro Ambiental Rural, or "CAR"), a land cadaster based on self-declaration of property boundaries, was created to monitor compliance with national forest laws. It has become an important enabling measure for sustainable supply chain initiatives like the Amazon Soy Moratorium. However, CAR enrollment is increasingly used to bolster illegal land claims, putting it at the heart of land grabbing dynamics. Self-declaration of properties in the CAR offers a unique situation to study land conflicts and their impact on land use decisions on a large scale. We quantified competing land claims among 846,420 registrations in the Brazilian Legal Amazon and applied a series of generalized linear mixed-effects models. We determined that CAR overlaps are more prevalent on larger registrations, in more densely settled areas, and in areas with less secure land tenure. We tested how landholders respond to land conflicts, finding significantly more deforestation and declared legal forest reserve on lands with multiple claims. CAR overlap results in an overestimation of forest reserves by up to 9.7 million hectares when considering double-counted and deforested areas of reserves, highlighting an overlooked form of Forest Code noncompliance. While the CAR continues to be used as evidence of land tenure, we conclude that the formalization of land claims through self-declarations is inadequate to decrease conflicts. CAR overlap information provides objective evidence of land conflict that authorities can leverage with field inspection to ensure peaceful occupation before issuing land titles.


Asunto(s)
Conservación de los Recursos Naturales , Brasil , Bosques , Humanos , Agricultura , Sistema de Registros , Población Rural , Monitoreo del Ambiente/métodos
2.
Chembiochem ; 25(4): e202300736, 2024 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-38195841

RESUMEN

PROTAC linker design remains mostly an empirical task. We employed the PRosettaC computational software in the design of sulfonyl-fluoride-based PROTACs targeting acyl protein thioesterase 1 (APT1). The software efficiently generated ternary complex models from empirically-designed PROTACs and suggested alkyl linkers to be the preferred type of linker to target APT1. Western blotting analysis revealed efficient degradation of APT1 and activity-based protein profiling showed remarkable selectivity of an alkyl linker-based PROTAC amongst serine hydrolases. Collectively, our data suggests that combining PRosettaC and chemoproteomics can effectively assist in triaging PROTACs for synthesis and providing early data on their potency and selectivity.

3.
BMC Vet Res ; 20(1): 63, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38388939

RESUMEN

BACKGROUND: The combined application of predatory fungi and antiparasitic drugs is a sustainable approach for the integrated control of animal gastrointestinal (GI) parasites. However, literature addressing the possible interference of antiparasitic drugs on the performance of these fungi is still scarce. This research aimed to assess the in vitro susceptibility of six native coccidicidal fungi isolates of the species Mucor circinelloides and one Mucor lusitanicus isolate to several antiparasitic drugs commonly used to treat GI parasites' infections in birds, namely anthelminthics such as Albendazole, Fenbendazole, Levamisole and Ivermectin, and anticoccidials such as Lasalocid, Amprolium and Toltrazuril (drug concentrations of 0.0078-4 µg/mL), using 96-well microplates filled with RPMI 1640 medium, and also on Sabouraud Agar (SA). RESULTS: This research revealed that the exposition of all Mucor isolates to the tested anthelminthic and anticoccidial drug concentrations did not inhibit their growth. Fungal growth was recorded in RPMI medium, after 48 h of drug exposure, as well as on SA medium after exposure to the maximum drug concentration. CONCLUSIONS: Preliminary findings from this research suggest the potential compatibility of these Mucor isolates with antiparasitic drugs for the integrated control of avian intestinal parasites. However, further in vitro and in vivo studies are needed to confirm this hypothesis.


Asunto(s)
Antiparasitarios , Mucor , Animales , Antiparasitarios/farmacología , Ivermectina/farmacología , Albendazol
4.
BMC Vet Res ; 20(1): 314, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39010064

RESUMEN

Eimeria spp. are the pathogen that causes coccidiosis, a significant disease that affects intensively reared livestock, especially poultry. Anticoccidial feed additives, chemicals, and ionophores have routinely been employed to reduce Eimeria infections in broiler production. Therefore, the shift to antibiotic-free and organic farming necessitates novel coccidiosis preventive strategies. The present study evaluated the effects of potential feed additives, liver free and chitosan, against Eimeria tenella infection in White Leghorn broiler female chickens. One hundred sixty-five 1-day-old White Leghorn broiler female chicks were divided into 11 groups (15 female chicks per group), including the positive control group (G1), the negative control group (G2), a chitosan-treated group (G3), a chitosan-treated-infected group (G4), the liver free-treated group (G5), the liver free-treated-infected group (G6), the liver free-and-chitosan-treated group (G7), the liver free-and-chitosan-infected group (G8), the therapeutic liver free-and-chitosan-treated-infected group (G9), the sulfaquinoxaline-treated group (G10), and the sulfaquinoxaline-treated-infected group (G11). Chitosan was fed to the chicks in G3 and G4 as a preventative measure at a dose of 250 mg/kg. The G5 and G6 groups received 1.5 mg/kg of Liverfree. The G7 and G8 groups received chitosan and Liverfree. The G10 and G11 groups were administered 2 g/L of sulfaquinoxaline. From the moment the chicks arrived at Foshan University (one-day-old chicks) until the completion of the experiment, all medications were given to them as a preventative measure. G8 did; however, receive chitosan and liver free as therapeutic supplements at 7 dpi. The current study showed that the combination of liver free and chitosan can achieve better prophylactic and therapeutic effects than either alone. In E. tenella challenged chickens, G8 and G9 chickens showed reduced oocyst shedding and lesion score, improved growth performance (body weight, body weight gain, feed intake, feed conversion ratio, and mortality rate), and cecal histology. The current study demonstrates that combining liver free and chitosan has superior preventive and therapeutic benefits than either alone, and they could also be used as alternative anticoccidial agents.


Asunto(s)
Alimentación Animal , Pollos , Quitosano , Coccidiosis , Coccidiostáticos , Eimeria tenella , Hígado , Enfermedades de las Aves de Corral , Animales , Quitosano/farmacología , Quitosano/uso terapéutico , Coccidiosis/veterinaria , Coccidiosis/tratamiento farmacológico , Coccidiosis/parasitología , Coccidiosis/prevención & control , Eimeria tenella/efectos de los fármacos , Enfermedades de las Aves de Corral/tratamiento farmacológico , Enfermedades de las Aves de Corral/parasitología , Enfermedades de las Aves de Corral/prevención & control , Femenino , Coccidiostáticos/uso terapéutico , Coccidiostáticos/farmacología , Hígado/efectos de los fármacos , Hígado/parasitología
5.
Parasitol Res ; 123(7): 267, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38990228

RESUMEN

Exsheathment is crucial in the transition from free-living to parasitic phase for most strongyle nematode species. A greater understanding of this process could help in developing new parasitic control methods. This study aimed to identify commonalities in response to exsheathment triggers (heat acclimation, CO2 and pH) in a wide range of species (Haemonchus contortus, Trichostrongylus spp., Cooperia spp., Oesophagostomum spp., Chabertia ovina, and members of the subfamily Ostertagiinae) from sheep, cattle and farmed deer. The initial expectation of similarity in pH requirements amongst species residing within the same organ was not supported, with unexpected pH preferences for exsheathment of Trichostrongylus axei, Trichostrongylus vitrinus, Trichostrongylus colubriformis and Cooperia oncophora. We also found differences between species in their response to temperature acclimation, with higher exsheathment in response to heat shock observed for H. contortus, Ostertagia ostertagi, T. axei, T. vitrinus and Oesophagostomum sikae. Furthermore, some species showed poor exsheathment under all experimental conditions, such as Cooperia curticei and the large intestinal nematodes C. ovina and Oesophagostomum venulosum. Interestingly, there were some significant differences in response depending on the host from which the parasites were derived. The host species significantly impacted on the exsheathment response for H. contortus, Teladorsagia circumcincta, T. vitrinus and T. colubriformis. Overall, the data showed variability between nematode species in their response to these in vitro exsheathment triggers, highlighting the complexity of finding a common set of conditions for all species in order to develop a control method based on triggering the exsheathment process prematurely.


Asunto(s)
Ciervos , Infecciones por Nematodos , Enfermedades de las Ovejas , Animales , Ciervos/parasitología , Bovinos , Ovinos/parasitología , Enfermedades de las Ovejas/parasitología , Infecciones por Nematodos/parasitología , Infecciones por Nematodos/veterinaria , Concentración de Iones de Hidrógeno , Nematodos/fisiología , Nematodos/clasificación , Enfermedades de los Bovinos/parasitología , Dióxido de Carbono , Parasitosis Intestinales/veterinaria , Parasitosis Intestinales/parasitología , Calor
6.
Health Promot Int ; 39(4)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39175415

RESUMEN

Cancer is one of the most important societal challenges in the world, with over 23 million new cases/year and 10 million deaths/year, that will only be properly tackled with a stronger focus on prevention. This calls for an informed population, aware of risk factors and willing to adopt preventive behaviors and early cancer screenings. For that purpose, 2' Life-changing minutes was created, the first ever televised Entertainment-Education series on cancer prevention. This study aims to evaluate the impact of 2' Life-changing minutes, a novel E-E format for cancer prevention, on knowledge gains and behavior changes. Two complementary studies were performed involving a total of 1314 participants: a test-screening (TS) study targeting potential viewers of the series, and a natural-screening (NS) study targeting those that spontaneously watched the series on television. We found (i) very high levels of appreciation and narrative engagement, and also willingness to see more episodes; (ii) statistically significant knowledge gains, ranging from 17% to 44%, on all four topics tested; (iii) evidence of effective behavior change. Regression analysis showed that narrative engagement was the best predictor of behavior change [NS: odds ratio (OR) = 3.38, 95% confidence interval (CI) = 1.70-6.74, p = 0.001; TS: OR = 2.05, 95% CI = 1.13-0.371, p = 0.018]. This study demonstrates the series' real impact and serves as a proof-of-concept for a novel strategy of cancer prevention that is based around compelling health narratives, rather than information or data, to engage viewers, increase knowledge and induce behavior change.


Asunto(s)
Detección Precoz del Cáncer , Conocimientos, Actitudes y Práctica en Salud , Promoción de la Salud , Neoplasias , Televisión , Humanos , Promoción de la Salud/métodos , Femenino , Masculino , Neoplasias/prevención & control , Persona de Mediana Edad , Adulto , Conductas Relacionadas con la Salud , Anciano
7.
Molecules ; 29(5)2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38474435

RESUMEN

Cervical cancer was considered the fourth most common cancer worldwide in 2020. In order to reduce mortality, an early diagnosis of the tumor is required. Currently, this type of cancer occurs mostly in developing countries due to the lack of vaccination and screening against the Human Papillomavirus. Thus, there is an urgent clinical need for new methods aiming at a reliable screening and an early diagnosis of precancerous and cancerous cervical lesions. Vibrational spectroscopy has provided very good results regarding the diagnosis of various tumors, particularly using Fourier transform infrared microspectroscopy, which has proved to be a promising complement to the currently used histopathological methods of cancer diagnosis. This spectroscopic technique was applied to the analysis of cryopreserved human cervical tissue samples, both squamous cell carcinoma (SCC) and non-cancer samples. A dedicated Support Vector Machine classification model was constructed in order to categorize the samples into either normal or malignant and was subsequently validated by cross-validation, with an accuracy higher than 90%.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias del Cuello Uterino , Femenino , Humanos , Carcinoma de Células Escamosas/patología , Neoplasias del Cuello Uterino/patología , Espectroscopía Infrarroja por Transformada de Fourier/métodos
8.
Acta Chir Belg ; : 1-12, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38607666

RESUMEN

OBJECTIVES: Liver trauma is common and can be treated non-operatively, through radiological embolisation, or surgically. Non-operative management (NOM) is preferred when possible, but specific criteria remain unclear. This retrospective study at a level I trauma centre assessed the evolution and outcomes of liver injury management over more than 20 years. METHODS: Data from January 1996 to June 2020 were analysed for liver trauma cases. Variables were evaluated, including the type of injury, diagnostic modalities, liver injury grade, transfer from other hospitals, treatment type, and length of hospital stay. Outcomes were assessed using soft (hospitalisation time and intensive care unit stay) and hard (mortality) endpoints. RESULTS: In total 406 patients were analysed, of which 375 (92.4%) had a blunt and 31 (7.6%) a penetrating liver trauma. Approximately one-third (31.2%) were hemodynamically unstable, although 78.8% had low-grade liver lesions. The initial treatment was non-operative in 72.9% of the patients (68.5% conservative, 4.4% interventional radiology). Blunt trauma was treated by surgery in 23.2% of the patients, while 74.2% in case of penetrating trauma. Overall mortality was 11.1% including death caused by associated lesions. The 24-h mortality was 5.7%. Indication for surgical treatment was determined by hemodynamic instability, high grade liver lesion, penetrating trauma, and associated lesions. CONCLUSIONS: Although the role of surgery in liver trauma management has strongly diminished over recent decades, hemodynamically unstable patients, high-grade lesions, penetrating trauma, and severe associated lesions are the main indications for surgery. In other situations, NOM by full conservative therapy or radiological embolisation seems effective.

9.
HPB (Oxford) ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39277435

RESUMEN

BACKGROUND: Major hepatectomy in perihilar cholangiocarcinoma (pCCA) patients with a small future liver remnant (FLR) risks posthepatectomy liver failure (PHLF). This study examines combined portal and hepatic vein embolisation (PVE/HVE) to increase preoperative FLR volume and potentially decrease PHLF rates. METHODS: In this retrospective, multicentre, observational study, data was collected from centres affiliated with the DRAGON Trials Collaborative and the EuroLVD registry. The study included pCCA patients who underwent PVE/HVE between July 2016 and January 2023. RESULTS: Following PVE/HVE, 28% of patients (9/32) experienced complications, with 22% (7/32) necessitating biliary interventions for cholangitis. The median degree of hypertrophy after a median of 16 days was 16% with a kinetic growth rate of 6.8% per week. 69% of patients (22/32) ultimately underwent surgical resection. Cholangitis after PVE/HVE was associated with unresectability. After resection, 55% of patients (12/22) experienced complications, of which 23% (5/22) were Clavien-Dindo grade III or higher. The 90-day mortality after resection was 0%. CONCLUSION: PVE/HVE quickly enhances the kinetic growth rate in pCCA patients. Cholangitis impairs chances on resection significantly. Resection after PVE/HVE is associated with low levels of 90-day mortality. The study highlights the potential of PVE/HVE in improving safety and outcomes in pCCA undergoing resection.

10.
Anal Chem ; 95(4): 2469-2477, 2023 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-36638233

RESUMEN

The first neutron diffraction study of in-situ anaerobic burning of human bones is reported, aiming at an interpretation of heat-induced changes in bone, which were previously detected by vibrational spectroscopy, including inelastic neutron scattering techniques. Structural and crystallinity variations were monitored in samples of the human femur and tibia, as well as a reference hydroxyapatite, upon heating under anaerobic conditions. Information on the structural reorganization of the bone matrix as a function of temperature, from room temperature to 1000 °C, was achieved. Noticeable crystallographic and domain size variations, together with O-H bond lengths and background variations, were detected. Above 700 °C, the inorganic bone matrix became highly symmetric, devoid of carbonates and organic constituents, while for the lower temperature range (<700 °C), a considerably lower crystallinity was observed. The present pilot study is expected to contribute to a better understanding of the heat-prompted changes in bone, which can be taken as biomarkers of the burning temperature. This information is paramount for bone analysis in forensic science as well as in archeology and may also have useful applications in other biomaterial studies.


Asunto(s)
Calefacción , Difracción de Neutrones , Humanos , Anaerobiosis , Proyectos Piloto , Huesos , Difracción de Rayos X
11.
Chembiochem ; 24(21): e202300418, 2023 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-37671979

RESUMEN

Intramembrane serine proteases (rhomboid proteases) are involved in a variety of biological processes and are implicated in several diseases. Here, we report 4-oxo-ß-lactams as a novel scaffold for inhibition of rhomboids. We show that they covalently react with the active site and that the covalent bond is sufficiently stable for detection of the covalent rhomboid-lactam complex. 4-Oxo-ß-lactams may therefore find future use as both inhibitors and activity-based probes for rhomboid proteases.


Asunto(s)
Endopeptidasas , beta-Lactamas , beta-Lactamas/farmacología , Serina Proteasas
12.
Clin Proteomics ; 20(1): 54, 2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-38017382

RESUMEN

BACKGROUND: This study investigates the proteomic landscapes of chromophobe renal cell carcinoma (chRCC) and renal oncocytomas (RO), two subtypes of renal cell carcinoma that together account for approximately 10% of all renal tumors. Despite their histological similarities and shared origins, chRCC is a malignant tumor necessitating aggressive intervention, while RO, a benign growth, is often subject to overtreatment due to difficulties in accurate differentiation. METHODS: We conducted a label-free quantitative proteomic analysis on solid biopsies of chRCC (n = 5), RO (n = 5), and normal adjacent tissue (NAT, n = 5). The quantitative analysis was carried out by comparing protein abundances between tumor and NAT specimens. Our analysis identified a total of 1610 proteins across all samples, with 1379 (85.7%) of these proteins quantified in at least seven out of ten LC‒MS/MS runs for one renal tissue type (chRCC, RO, or NAT). RESULTS: Our findings revealed significant similarities in the dysregulation of key metabolic pathways, including carbohydrate, lipid, and amino acid metabolism, in both chRCC and RO. Compared to NAT, both chRCC and RO showed a marked downregulation in gluconeogenesis proteins, but a significant upregulation of proteins integral to the citrate cycle. Interestingly, we observed a distinct divergence in the oxidative phosphorylation pathway, with RO showing a significant increase in the number and degree of alterations in proteins, surpassing that observed in chRCC. CONCLUSIONS: This study underscores the value of integrating high-resolution mass spectrometry protein quantification to effectively characterize and differentiate the proteomic landscapes of solid tumor biopsies diagnosed as chRCC and RO. The insights gained from this research offer valuable information for enhancing our understanding of these conditions and may aid in the development of improved diagnostic and therapeutic strategies.

13.
J Urban Health ; 100(6): 1234-1245, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37947996

RESUMEN

Rising ambient temperatures due to climate change will impact both indoor temperatures and heating and cooling utility costs. In traditionally colder climates, there are potential tradeoffs in how to meet the reduced heating and increased cooling demands, and issues related to lack of air conditioning (AC) access in older homes and among lower-income populations to prevent extreme heat exposure. We modeled a typical multi-family home in Boston (MA) in the building simulation program EnergyPlus to assess indoor temperature and energy consumption in current (2020) and projected future (2050) weather conditions. Selected households were those without AC (no AC), those who ran AC sometimes (some AC), and those with sufficient resources to run AC always (full AC). We considered stylized cooling subsidy policies that allowed households to move between groups, both independently and in conjunction with energy efficiency retrofits. Results showed that future weather conditions without policy changes yielded an increase in indoor summer temperatures of 2.1 °C (no AC), increased cooling demand (range: 34-50%), but led to a decrease in net yearly total utility costs per apartment (range: - $21 to - $38). Policies that allowed households to move to greater AC utilization yielded average indoor summer temperature decreases (- 3.5 °C to - 6.2 °C) and net yearly total utility increases (range: + $2 to + $94) per apartment unit, with greater savings for retrofitted homes primarily due to large decreases in heating use. Our model results reinforce the importance of coordinated public policies addressing climate change that have an equity lens for both health and climate goals.


Asunto(s)
Calor Extremo , Vivienda , Humanos , Anciano , Temperatura , Boston , Estaciones del Año
14.
Mol Cell Proteomics ; 20: 100093, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33992776

RESUMEN

The sulfated glycosaminoglycans (GAGs) are long, linear polysaccharide chains that are typically found as the glycan portion of proteoglycans. These GAGs are characterized by repeating disaccharide units with variable sulfation and acetylation patterns along the chain. GAG length and modification patterns have profound impacts on growth factor signaling mechanisms central to numerous physiological processes. Electron activated dissociation tandem mass spectrometry is a very effective technique for assigning the structures of GAG saccharides; however, manual interpretation of the resulting complex tandem mass spectra is a difficult and time-consuming process that drives the development of computational methods for accurate and efficient sequencing. We have recently published GAGfinder, the first peak picking and elemental composition assignment algorithm specifically designed for GAG tandem mass spectra. Here, we present GAGrank, a novel network-based method for determining GAG structure using information extracted from tandem mass spectra using GAGfinder. GAGrank is based on Google's PageRank algorithm for ranking websites for search engine output. In particular, it is an implementation of BiRank, an extension of PageRank for bipartite networks. In our implementation, the two partitions comprise every possible sequence for a given GAG composition and the tandem MS fragments found using GAGfinder. Sequences are given a higher ranking if they link to many important fragments. Using the simulated annealing probabilistic optimization technique, we optimized GAGrank's parameters on ten training sequences. We then validated GAGrank's performance on three validation sequences. We also demonstrated GAGrank's ability to sequence isomeric mixtures using two mixtures at five different ratios.


Asunto(s)
Glicosaminoglicanos/química , Programas Informáticos , Algoritmos , Modelos Teóricos , Espectrometría de Masas en Tándem
15.
Parasitol Res ; 122(2): 435-440, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36434319

RESUMEN

At the end of the nineteenth century, massive population declines were observed in carnivores due to the emergence of infectious diseases. This study aims to investigate, by means of coprological analysis, the prevalence and intensity of the parasites that infect the endangered Iberian wolf Canis lupus signatus and two mesocarnivores (the red fox Vulpes vulpes and the stone marten Martes foina) in Central Portugal. In total, 67.2% of the samples screened were infected; Toxascaris leonina (40.6%) was the parasite with the highest prevalence, followed by Ancylostomatidae and Eimeria spp. (28.1%). Eimeria spp. was found in stone marten with the highest infection rate (37,800 OPG), followed by T. leonina (10,100 EPG) in a red fox sample. Moderate to high levels of parasitic infections were identified in 73.3% of red foxes from the western area. Our results highlight the possibility of cross-infection among these carnivore species and cross-contamination in the wildlife-livestock-human interface.


Asunto(s)
Carnívoros , Mustelidae , Lobos , Animales , Humanos , Lobos/parasitología , Portugal/epidemiología , Zorros/parasitología , Animales Salvajes , Mustelidae/parasitología
16.
Health Promot Int ; 38(3)2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37326410

RESUMEN

Cancer is a primary societal challenge worldwide, with over 23 million new cases/year, and 10 million deaths/year. Estimates of preventable cancer deaths rise as high as 70%, but such estimates rely heavily on individual behaviors, which in turn are correlated with knowledge and attitudes towards health and cancer. This paper describes the iterative evidence-based development of the first entertainment-education series on cancer prevention to be televised, and reports its effectiveness evaluation. A nominal group defined the guiding principles that were translated into key characteristics for a series named '2' Life-changing minutes'. Pilot episodes were produced and evaluated in two complementary studies-a focus group study with medical doctors and a survey study with prospective viewers. Results from these studies guided the optimization and production of the full series, which was broadcast on national public TV, in prime time. An evaluation study was performed afterwards with naturally-occurring viewers and results show audience reach on par with purely entertainment series, that health messages can be clearly conveyed through fictional narratives, and that the series has high levels of appreciation and health promotion potential. '2' Life-changing minutes' constitutes a novel and effective proposal for health promotion, that challenges the primacy of information and statistics still common in health communication, with a new format based on stories, characters and social contexts to successfully promote health.


Asunto(s)
Promoción de la Salud , Neoplasias , Humanos , Educación en Salud/métodos , Televisión , Portugal , Estudios Prospectivos , Neoplasias/prevención & control
17.
BMC Surg ; 23(1): 296, 2023 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-37775737

RESUMEN

BACKGROUND: The treatment of borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) has evolved with a wider application of neoadjuvant chemotherapy (NACHT). The aim of this study was to identify predictive factors for survival in BR and LA PDAC. METHODS: Clinicopathologic data of patients with BR and LA PDAC who underwent surgical exploration between January 2011 and June 2021 were retrospectively collected. Survival from the date of surgery was estimated using the Kaplan-Meier method. Simple and multiple Cox proportional hazards models were fitted to identify factors associated with survival. Surgical resection was analyzed in combination with the involvement of lymph nodes as this last was only known after a formal resection. RESULTS: Ninety patients were surgically explored (BR: 45, LA: 45), of which 51 (57%) were resected (BR: 31, LA: 20). NACHT was administered to 43 patients with FOLFIRINOX being the most frequent regimen applied (33/43, 77%). Major complications (Clavien-Dindo grade III and IV) occurred in 7.8% of patients and 90-day mortality rate was 3.3%. The median overall survival since surgery was 16 months (95% CI 12-20) in the group which underwent surgical resection and 10 months (95% CI 7-13) in the group with an unresectable tumor (p=0.001). Cox proportional hazards models showed significantly lower mortality hazard for surgical resection compared to no surgical resection, even after adjusting for National Comprehensive Cancer Network  (NCCN) classification and administration of NACHT [surgical resection with involved lymph nodes vs no surgical resection (cHR 0.49; 95% CI 0.29-0.82; p=0.007)]. There was no significant difference in survival between patients with BR and LA disease (cHR= 1.01; 95% CI 0.63-1.62; p=0.98). CONCLUSIONS: Surgical resection is the only predictor of survival in patients with BR and LA PDAC, regardless of their initial classification as BR or LA. Our results suggest that surgery should not be denied to patients with LA PDAC a priori. Prospective studies including patients from the moment of diagnosis are required to identify biologic and molecular markers which may allow a better selection of patients who will benefit from surgery.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Estudios Prospectivos , Fluorouracilo , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/patología , Terapia Neoadyuvante , Neoplasias Pancreáticas
18.
Int J Mol Sci ; 24(8)2023 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-37108046

RESUMEN

This study examines the influence of mefenamic acid on the physical and chemical properties of silica aerogels, as well as its effect on the sorption characteristics of the composite material. Solid state magic angle spinning nuclear magnetic resonance (MAS NMR) and high-pressure 13C NMR kinetic studies were conducted to identify the presence of mefenamic acid and measure the kinetic rates of CO2 sorption. Additionally, a high-pressure T1-T2 relaxation-relaxation correlation spectroscopy (RRCOSY) study was conducted to estimate the relative amount of mefenamic acid in the aerogel's pores, and a high-pressure nuclear Overhauser effect spectoscopy (NOESY) study was conducted to investigate the conformational preference of mefenamic acid released from the aerogel. The results indicate that mefenamic acid is affected by the chemical environment of the aerogel, altering the ratio of mefenamic acid conformers from 75% to 25% in its absence to 22% to 78% in the presence of aerogel.


Asunto(s)
Ácido Mefenámico , Dióxido de Silicio , Cinética , Espectroscopía de Resonancia Magnética/métodos , Imagen por Resonancia Magnética
19.
Int J Mol Sci ; 24(3)2023 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-36768221

RESUMEN

Regarding the development of new antineoplastic agents, with a view to assess the selective antitumoral potential which aims at causing irreversible damage to cancer cells while preserving the integrity of their healthy counterparts, it is essential to evaluate the cytotoxic effects in both healthy and malignant human cell lines. In this study, a complex with two Pd(II) centers linked by the biogenic polyamine spermine (Pd2Spm) was tested on healthy (PNT-2) and cancer (LNCaP and PC-3) prostate human cell lines, using cisplatin as a reference. To understand the mechanisms of action of both cisplatin and Pd2Spm at a molecular level, Fourier Transform Infrared (FTIR) and Raman microspectroscopies were used. Principal component analysis was applied to the vibrational data, revealing the major metabolic changes caused by each drug, which were found to rely on DNA, lipids, and proteins, acting as biomarkers of drug impact. The main changes were observed between the B-DNA native conformation and either Z-DNA or A-DNA, with a higher effect on lipids having been detected in the presence of cisplatin as compared to Pd2Spm. In turn, the Pd-agent showed a more significant impact on proteins.


Asunto(s)
Antineoplásicos , Neoplasias de la Próstata , Masculino , Humanos , Cisplatino/farmacología , Antineoplásicos/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Espermina/farmacología , Espermina/metabolismo , Lípidos , Espectroscopía Infrarroja por Transformada de Fourier
20.
Molecules ; 28(4)2023 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-36838683

RESUMEN

A dinuclear Pt(II) complex with putrescine as bridging polyamine ligand ([Pt2Put2(NH3)4]Cl4) was synthesized and assessed as to its potential anticancer activity against a human non-small cell lung cancer line (A549), as well as towards non-cancer cells (BEAS-2B). This effect was evaluated through in vitro cytotoxicity assays (MTT and SRB) coupled to microFTIR and microRaman spectroscopies, the former delivering information on growth-inhibiting and cytotoxic abilities while the latter provided very specific information on the metabolic impact of the metal agent (at the sub-cellular level). Regarding cancer cells, a major impact of [Pt2Put2(NH3)4]Cl4 was evidenced on cellular proteins and lipids, as compared to DNA, particularly via the Amide I and Amide II signals. The effect of the chelate on non-malignant cells was lower than on malignant ones, evidencing a promising low toxicity towards healthy cells.


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Platino (Metal)/farmacología , Línea Celular Tumoral , Antineoplásicos/farmacología
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