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Omarigliptin (OMG) is an antidiabetic drug indicated for the treatment of type 2 diabetes mellitus. Forced degradation studies are practical experiments to evaluate the stability of drugs and to establish degradation profiles. Herein, we present the investigation of the degradation products (DPs) of OMG formed under various stress conditions. OMG was subjected to hydrolytic (alkaline and acidic), oxidative, thermal, and photolytic forced degradation. A stability-indicating ultra-fast liquid chromatography method was applied to separate and quantify OMG and its DPs. Five DPs were adequately separated and detected in less than 6 min, while other published methods detected four DPs. MS was applied to identify and obtain information on the structural elucidation of the DPs. Three m/z DPs confirmed previously published research, and two novel DPs were described in this paper. The toxicity of OMG and its DPs were investigated for the first time using in vitro cytotoxicity assays, and the sample under oxidative conditions presented significant cytotoxicity. Based on the results from forced degradation studies, OMG was found to be labile to hydrolysis, oxidation, photolytic, and thermal stress conditions. The results of this study contribute to the quality control and stability profile of OMG.
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Estabilidade de Medicamentos , Compostos Heterocíclicos com 2 Anéis , Piranos , Cromatografia Líquida de Alta Pressão/métodos , Piranos/química , Piranos/análise , Piranos/toxicidade , Compostos Heterocíclicos com 2 Anéis/química , Compostos Heterocíclicos com 2 Anéis/análise , Compostos Heterocíclicos com 2 Anéis/toxicidade , Espectrometria de Massas/métodos , Humanos , Sobrevivência Celular/efeitos dos fármacos , Reprodutibilidade dos Testes , Hipoglicemiantes/química , Hipoglicemiantes/análise , Oxirredução , Modelos LinearesRESUMO
Global environmental concerns drive research toward the development of new eco-friendly compounds to replace pollutant chemicals. This study focuses on optimizing the production of trehalose lipids (TLs), which are glycolipid biosurfactants (BS) with various applications like antimicrobial or surface tension reduction. New microorganism sources, growth conditions, medium composition, purification conditions, and physicochemical properties of TLs are studied. Addressing a microscale approach, TLs production was successfully achieved using Rhodotorula sp. and Rhodococcus erythropolis to compare, with different media compositions including glucose-based and salt media supplemented with glycerol, glucose, n-hexadecane, n-dodecane. Liquid-liquid extraction using ethyl acetate and methanol was employed for compound extraction, followed by characterization using analytical methods such as Thin layer chromatography (TLC), High performance liquid chromatography (HPLC), and UHPLC. The produced TLs exhibited a minimum surface tension of 47 mN/m and a critical micellar concentration of 4.4 mg/mL. This study also identified Rhodotorula sp. as a new sustainable producer of TLs with improved productivity.
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Rhodotorula , Trealose , Glicolipídeos , Micelas , Glucose , Tensoativos/químicaRESUMO
Glioblastoma (GBM) is the most lethal and common malignant primary brain tumor in adults. An important feature that supports GBM aggressiveness is the unique composition of its extracellular matrix (ECM). Particularly, fibronectin plays an important role in cancer cell adhesion, differentiation, proliferation, and chemoresistance. Thus, herein, a hydrogel with mechanical properties compatible with the brain and the ability to disrupt the dynamic and reciprocal interaction between fibronectin and tumor cells was produced. High-molecular-weight hyaluronic acid (HMW-HA) functionalized with the inhibitory fibronectin peptide Arg-Gly-Asp-Ser (RGDS) was used to produce the polymeric matrix. Liposomes encapsulating doxorubicin (DOX) were also included in the hydrogel to kill GBM cells. The resulting hydrogel containing liposomes with therapeutic DOX concentrations presented rheological properties like a healthy brain. In vitro assays demonstrated that unmodified HMW-HA hydrogels only caused GBM cell killing after DOX incorporation. Conversely, RGDS-functionalized hydrogels displayed per se cytotoxicity. As GBM cells produce several proteolytic enzymes capable of disrupting the peptide-HA bond, we selected MMP-2 to illustrate this phenomenon. Therefore, RGDS internalization can induce GBM cell apoptosis. Importantly, RGDS-functionalized hydrogel incorporating DOX efficiently damaged GBM cells without affecting astrocyte viability, proving its safety. Overall, the results demonstrate the potential of the RGDS-functionalized hydrogel to develop safe and effective GBM treatments.
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Doxorrubicina , Fibronectinas , Glioblastoma , Ácido Hialurônico , Hidrogéis , Oligopeptídeos , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Doxorrubicina/farmacologia , Doxorrubicina/química , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Fibronectinas/metabolismo , Fibronectinas/antagonistas & inibidores , Hidrogéis/química , Linhagem Celular Tumoral , Ácido Hialurônico/química , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Lipossomos/química , Apoptose/efeitos dos fármacos , Metaloproteinase 2 da Matriz/metabolismoRESUMO
In Portugal, there are over 7800 children with life-limiting conditions. The context of pediatric palliative care represents a complex and distressing experience for families. Compared to parental caregivers and healthy siblings, grandparents are underexplored in the literature and clinical practice. The aim of the present study is to propose a psychological experience assessment tool of grandparents in this context. It consists of a sociodemographic and clinical data sheet and a semi-structured interview based on sharing a testimony with other grandparents. On the basis of the latter, 10 dimensions were explored through the grandparents' own perspective: representation of the illness; representation of the sick grandchild; changes in routine and life; family impact; grandparents' contributions to the family system; social support and coping strategies; emotional impact; triple concern; needs identification; and post-traumatic growth. The tool can be used in person or remotely and may be combined with other instruments. Its application enables a personalized identification of needs and challenges for each family, promoting the adjustment of the clinical intervention to their wellbeing and resilience from an eco-systemic perspective. The clinical tool is presented in detail and its importance in the context of research and systemic intervention is discussed.
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Cardiovascular diseases, considered the deadliest worldwide by the World Health Organization (WHO), lack effective therapies for regenerating cardiomyocytes. With their self-renewal and pluripotency capabilities, stem cell therapies are increasingly used in precision medicine. Induced pluripotent stem cells (iPSCs) are a promising alternative to embryonic stem cells. Good Manufacturing Practice (GMP) principles are not yet adapted for large-scale production of iPSCs. Additionally, the quality risk for iPSC products may not always be possible to eliminate, potentially jeopardizing the health of patients. This review aims to identify critical quality attributes (CQAs) for iPSC-derived cardiomyocytes (iPSC-CMs) for the development of cardiovascular therapy to ensure compliance with regulations and safety for patients. To attain these goals, the literature review was conducted with articles related to iPSCs and iPSC-CM therapies, legislation, and regulatory guidelines of the European Medicines Agency (EMA), Food and Drug Administration (FDA), and Pharmaceuticals and Medical Devices Agency (PMDA). In conclusion, additional regulations and guidelines are needed to monitor differentiation, maturation, and tumorigenicity. GMP-compliant cell banks and fast-track approval systems may increase accessibility for patients.
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Células-Tronco Pluripotentes Induzidas , Miócitos Cardíacos , Humanos , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Diferenciação Celular , Animais , Pesquisa Translacional BiomédicaRESUMO
Cannabis has been used in rheumatic diseases as therapy for chronic pain or inflammatory conditions. Herein, the authors systematically review the rheumatological diseases in which cannabis has been studied: systemic sclerosis, fibromyalgia, osteoarthritis, rheumatoid arthritis, osteoporosis, polymyalgia rheumatica, gout, dermatomyositis, and psoriatic arthritis. We systematically searched PubMed for articles on cannabis and rheumatic diseases between 1966 and March 2023. Twenty-eight articles have been selected for review. Most of them (n=13) were on fibromyalgia and all of them but one showed important reduction in pain; sleep and mood also improved. On rheumatoid arthritis, two papers displayed decrease in pain and in one of them a reduction in inflammatory parameters was found. In scleroderma there was a case description with good results, one study on local use for digital ulcers also with good outcomes and a third one, that disclosed good results for skin fibrosis. In dermatomyositis a single study showed improvement of skin manifestations and in osteoarthritis (3 studies) this drug has demonstrated a good analgesic effect. Several surveys (n=5) on the general use of cannabis showed that rheumatological patients (mixed diseases) do use this drug even without medical supervision. The reported side effects were mild. In conclusion, cannabis treatment is an interesting option for the treatment of rheumatological diseases that should be further explored with more studies.
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Coronary vasospasm is a well-recognized cause of angina (also known as Prinzmetal angina) and a common cause of admissions to the emergency department and coronary intensive care units. It is however an uncommon cause of cardiac arrest. We describe a patient with multiple episodes of chest pain followed by cardiac arrest in pulseless electrical activity (PEA) due to coronary vasospasm. Telemetry and electrocardiography showed ST-segment elevation followed by PEA. Each event was short-lived and resolved after a maximum of six minutes of advanced life support measures. The patient was started on treatment with a dihydropyridine calcium channel blocker (CCB) and nitroglycerin patch with no further episodes recorded to date.
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Hemodialysis catheters are frequently used for vascular access in end-stage chronic kidney disease patients lacking mature arteriovenous fistula. The incidence of infective endocarditis in hemodialysis patients is higher than in the general population and is associated with severe and potentially life-threatening complications. A high index of suspicion is imperative for early diagnosis and timely intervention to enhance the prognosis of this high-mortality condition. Imaging studies, like transthoracic and transesophageal echocardiography, are crucial for prompt diagnosis. We present a case of a 36-year-old woman undergoing hemodialysis, whose prolonged use of a permanent catheter led to the development of infective endocarditis complicated with septic pulmonary embolism. Our case report presents an example of right atrial endocarditis with a poor outcome due to delayed diagnosis.
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PURPOSE: This systematic review with meta-analysis aims to analyze the effects of different types of exercise on cognition, neuroprotective and neuroinflammatory blood markers in older adults with mild cognitive impairment (MCI). METHODS: Relevant studies were identified using PubMED, SPORTDiscuss, Web of Science, Scopus, and PsycInfo databases. Methodological quality assessment of the studies was done with modified Downs and Black checklist. Data obtained from the included studies was analyzed using Comprehensive Meta-Analysis 4.0 software and results were reported using the random effects method. RESULTS: A total of twenty-three studies were identified. The findings were summarized as change in cognitive function after the exercise interventions in general and after each type of exercise. On average, the exercise intervention revealed an effect size (ES): 1.165; 0.741 to 1.589 (95% Confidence Interval (CI); p < 0.001); aerobic exercise ES: 1.442; 0.624 to 2.260 (95 %CI); p = 0.001; Multimodal ES: 0,856; 0.366 to 1.346 (95 % CI); p = 0.001 and resistance exercise ES: 1.229; 0.339 to 2.120 (95 % CI); p = 0.007. In addition, we observed significant small ES: -0.475; -0.817 to -0.134 (95 %CI); p = 0.006, I2= 0 %; τ2 = 0 of exercise effects on Tumor Necrosis Factor-α (TNF-α) and non-significant large ES:0.952; -0.238 to 2.142 (95 %CI); p = 0.117 on Brain Derived Neurotrophic Factor (BDNF) in persons with MCI. CONCLUSION: The present study revealed the existence of a large positive effect of overall exercise intervention on cognitive function and a small effect on TNF-α in old people with MCI. Additionally, this study demonstrates that aerobic and resistance exercises had similar larger positive effects and were better than multimodal exercise on increasing cognition in older persons with MCI.
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Previous studies have investigated the effects of different combined training programs involving traditional resistance training and aerobic exercise on hemodynamic parameters and arterial stiffness in older adults. However, little is known about the impact of power training combined with endurance training on these variables in hypertensive older adults. Therefore, this study aimed to investigate the effects of dynamic power training with elastic bands combined with endurance training on arterial stiffness and hemodynamic parameters in hypertensive older adults. Twenty-six participants were randomly assigned to the control group (CG; nâ=â13) and the intervention group (nâ=â13). IG participants performed power training with elastic bands combined with endurance training twice a week for 8âweeks. Pulse pressure, central pulse pressure, pulse wave velocity, SBP, DBP, central SBP, and central DBP were assessed before and after 8âweeks using the triple pulse wave velocity method. Pulse pressure, central pulse pressure, pulse wave velocity, SBP, DBP, central SBP, and central DBP significantly improved after 8âweeks of intervention (Pâ<â0.05). These findings indicate that power training with elastic bands combined with endurance training reduces arterial stiffness and significantly improves hemodynamic parameters in older adults diagnosed with grade 1 hypertension. In addition, underscores the potential of this approach as a promising strategy for the management of hypertension in older adults.
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Treino Aeróbico , Hipertensão , Treinamento Resistido , Humanos , Idoso , Análise de Onda de Pulso , Hipertensão/terapia , Pressão SanguíneaRESUMO
In contrast to traditional beach profiling methods like topographic surveys and GNSS, which pose significant challenges in terms of cost and time, this research underscores the efficiency, cost-effectiveness, and simplicity of terrestrial photogrammetry employing the Structure from Motion-Multi View Stereo (SfM-MVS) method. Notably, this approach enables the utilization of commonplace devices such as smartphones for data capture. The methodology integrates a 12-megapixel camera for image acquisition, processed through Agisoft Metashape Professional software, and validated for accuracy using ground control points (GCPs) and checkpoints (CKPs) calibrated via GNSS. Findings reveal substantial disparities in positional accuracy according to the Ground Control Points distribution. The study underscores the critical role of strategically distributing GCPs and CKPs in effectively mapping coastal areas, thus affirming the potential of SfM-MVS as a powerful and accessible tool for coastal monitoring initiatives. This research contributes significantly to advancing the efficiency and accessibility of beach profile monitoring, offering invaluable insights for researchers and practitioners in coastal management and environmental conservation efforts.â¢A simplified beach profile modeling methodology is proposed.â¢The method is faster and more cost-effective than traditional surveys (RTK GNSS, lidar, RPA).â¢The study highlights the importance of GCP and CKP distribution in enhancing SfM-MVS accuracy for coastal mapping.
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OBJECTIVE: It is known that exposure to air pollution is associated with an increased risk for cardiovascular and respiratory diseases. This review aimed to summarise observational studies on the impact of short and long-term exposure to ambient air pollution on prevalence of hospitalisations and/or emergency department visits caused by respiratory diseases in children and adolescents. SOURCES: Pubmed, Scopus, Embase and Cochrane Library databases were searched for the years 2018 to December 2022, including studies in any language. SUMMARY OF THE FINDINGS: A total of 15 studies published between 2018 and 15 January 2022 were included in this review. PM2.5 was the most type of particulate matter studied. Short-term exposure to PM2,5, PM10, NO2, SO2 and O3, even at concentrations less than the current health-based guidelines, was significantly correlated with increased risk of outpatient/hospital visits and hospitalisations for respiratory diseases by children. CONCLUSIONS: Our findings emphasise the importance and urgency of long-term control of air pollution and pollution-related diseases, especially among children and adolescents. There is a need for further research employing more homogeneous methodologies for assessing exposure and outcome measurements, in order to enable systematic reviews with meta-analysis.
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PURPOSE: To characterize the occurrence of diabetic macular edema and the presence of abnormal retinal fluid accumulation in nonproliferative diabetic retinopathy (NPDR). METHODS: In this two-year prospective study, a total of 122 eyes with diabetes type 2 underwent optical coherence tomography (OCT) and OCT-Angiography in association with OCT-Fluid imaging, a novel algorithm of OCT analysis allowing quantification of abnormal accumulation of fluid in the retina through low optical reflectivity ratios (LOR). Early Treatment Diabetic Retinopathy Study (ETDRS) grading for diabetic retinopathy (DR) severity assessment was performed using 7-field color fundus photography. Best corrected visual acuity was also recorded. RESULTS: During the 2-year follow-up, 23 eyes (19%) developed central-involved diabetic macular edema (CI-DME) and 2 eyes (2%) developed clinically significant macular edema (CSME). In the two-year period of the study, eyes that developed CI-DME showed a progressive increase in central retinal thickness (CRT) (ß = 7.7 ± 2.1â µm/year, p < 0.001) and in LOR values (ß = 0.009 ± 0.004 ratio/year, p = 0.027). The increase in CRT and abnormal retinal fluid, represented by increased LOR ratios, are associated with increased retinal perfusion in the deep capillary plexus (DCP) (skeletonized vessel density, p = 0.039). In contrast, the eyes with CSME showed decreased retinal perfusion and abnormal fluid located in the outer layers of the retina. CONCLUSIONS: CI-DME and CSME appear to represent different entities. Eyes with CI-DME show increases in abnormal retinal fluid associated with increased retinal vascular perfusion in the DCP. Eyes with CSME are apparently associated with decreased retinal vascular perfusion in the DCP and abnormal fluid in the outer retina.
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To evaluate the polymerization shrinkage stress and cuspal strain (CS) generated in an artificial (typodont) and in a natural tooth using different resin composites. Twenty artificial and 20 extracted natural molars were selected. Each tooth was prepared with a 4x4 mm MOD cavity. The natural and typodont teeth were divided into four experimental groups (n=10), according to the resin composite used: Filtek Z100 (3M Oral Care) and Beautifil II LS (Shofu Dental). The cavities were filled using two horizontal increments and the CS (µS) was measured by the strain gauge method. Samples were sectioned into stick-shaped specimens and the bond strength (BS) (MPa) was evaluated using a microtensile BS test. Shrinkage stress and CS were analyzed using 3D finite element analysis. No difference was found between the type of teeth for the CS as shown by the pooled averages: Natural tooth: 541.2 A; Typodont model: 591.4 A. Filtek Z100 CS values were higher than those obtained for Beautifil II LS, regardless of the type of teeth. No statistical difference was found for the BS data. Adhesive failures were more prevalent (79.9%). High shrinkage stress values were observed for Filtek Z100 resin, regardless of tooth type. The CS of typodont teeth showed a shrinkage stress effect, generated during restoration, equivalent to that of natural teeth.
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Resinas Compostas , Análise do Estresse Dentário , Análise de Elementos Finitos , Teste de Materiais , Polimerização , Estresse Mecânico , Resistência à Tração , Resinas Compostas/química , Humanos , Valores de Referência , Propriedades de Superfície , Reprodutibilidade dos Testes , Colagem Dentária/métodos , Coroa do DenteRESUMO
Purpose: To identify progression of nonproliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes by combining optical coherence tomography angiography (OCTA) metrics and color fundus photography (CFP) images. Methods: This study was a post hoc analysis of a prospective longitudinal cohort study (CORDIS, NCT03696810) with 2-year duration. This study enrolled 122 eyes. Ophthalmological examinations included OCTA and CFP. OCTA metrics included skeletonized vessel density (SVD) and perfusion density (PD) at the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Microaneurysm turnover analysis and Early Treatment Diabetic Retinopathy Study (ETDRS) grading for diabetic retinopathy (DR) severity assessment were performed on 7-field CFP. Results: Eyes graded as ETDRS level 20 showed significant capillary nonperfusion predominantly in the inner ring area in the SCP (P < 0.001), whereas eyes graded as ETDRS level 35 and ETDRS levels 43 and 47 showed significant capillary nonperfusion in both the SCP and DCP in both inner and outer rings (P < 0.001). When evaluating rates of progression in capillary nonperfusion for the 2-year period of follow-up, changes were found predominantly in the DCP for SVD and PD and were better identified in the outer ring area. Microaneurysm turnover contributes to the characterization of NPDR progression by discriminating ETDRS level 35 from ETDRS levels 43 and 47 (P < 0.001), which could not be achieved using only OCTA metrics. Conclusions: Patterns of progression of NPDR can be identified combining OCTA examinations of the superficial and deep retinal capillary plexi of central retina and determination of microaneurysm turnover from fundus photographs. Translational Relevance: Our study reports results from a registered clinical trial that advances understanding of disease progression in NPDR.
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Retinopatia Diabética , Progressão da Doença , Angiofluoresceinografia , Vasos Retinianos , Tomografia de Coerência Óptica , Humanos , Retinopatia Diabética/diagnóstico por imagem , Retinopatia Diabética/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Tomografia de Coerência Óptica/métodos , Estudos Prospectivos , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Idoso , Angiofluoresceinografia/métodos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , FotografaçãoRESUMO
Turner syndrome (TS) is caused by a complete or partial absence of an X or Y chromosome, including chromosomal mosaicism, affecting 1 in 2500 female live births. Sister chromatid exchange (SCE) is used as a sensitive indicator of spontaneous chromosome instability. Cells from mosaic patients constitute useful material for SCE evaluations as they grow under the influence of the same genetic background and endogenous and exogenous factors. We evaluated the proliferation dynamics and SCE frequencies of 45,X and 46,XN cells of 17 mosaic TS patients. In two participants, the 45,X cells exhibited a proliferative disadvantage in relation to 46,XN cells after 72 h of cultivation. The analysis of the mean proliferation index (PI) showed a trend for a significant difference between the 45,X and 46,X+der(X)/der(Y) cell lineages; however, there were no intra-individual differences. On the other hand, mean SCE frequencies showed that 46,X+der(X) had the highest mean value and 46,XX the lowest, with 45,X occupying an intermediate position among the lineages found in at least three participants; moreover, there were intra-individual differences in five patients. Although 46,X+der(X)/der(Y) cell lineages, found in more than 70% of participants, were the most unstable, they had a slightly higher mean PI than the 45,X cell lineages in younger (≤17 years) mosaic TS participants. This suggests that cells with a karyotype distinct from 45,X may increase with time in mosaic TS children and adolescents.
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Zootechnical data is a big challenge in the extensive rearing system of Brazilian locally adapted breeds once smallholdings with limited resources and funds rear them. So, information on Brazil's breeding system of locally adapted breeds is still scarce; this situation is more challenging for equine breeds. The present study aimed to describe the local rearing systems and the phenotypic profile of the Nordestino horse breed in Paraíba state and contribute to breed conservation. Data from males (entire and castrated) and females from 50 municipalities in Paraíba state were used. Two hundred sixty-nine animals (111 females, 121 castrated males, and 37 entire males) from 129 breeders were analyzed. A questionnaire consisting of direct and objective questions was applied to understand the breeding system adopted. There was a predominance of the extensive breeding system (85%), which reflects the adaptation of the Nordestino Horse to the region's natural conditions. The lower frequency of use of cultivated pastures may be related to issues of economic viability since the maintenance of cultivated pastures may require additional investments compared to the use of natural pastures. Entire males had a minimum withers height (WH) of 135 cm. Of the 11 morphometric measurements, only five were considered discriminating by the stepwise analysis. The remaining Nordestino horses have morphological characteristics within the breed standard.
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Alérgenos , Pesos e Medidas Corporais , Masculino , Feminino , Animais , Cavalos , BrasilRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Agaricus blazei Murill (AbM) is one of the main mushrooms used for medicinal purposes. The use of AbM in the preparation of teas is widespread mainly in Asian countries, while in Brazil it is used as a functional food to combat inflammatory diseases and cancer. AIM OF THE STUDY: The main focus of this study was the characterization of the chemical profile of the hydroalcoholic extract of Agaricus blazei Murill (AbE), as well as the evaluation of its cytotoxic and anti-inflammatory potential using human neutrophils. MATERIALS AND METHODS: The extract was prepared by dynamic maceration using a mixture of ethanol and water (70/30, v v-1) as solvent. The chemical profile characterization was carried out by 2D NMR and GC-MS techniques. The cytotoxicity of AbE was evaluated through studies of hemolytic potential, cell viability and membrane integrity. The anti-inflammatory activity was analyzed by a PMA-induced neutrophil degranulation assay. RESULTS: Chemical analysis of AbE revealed the presence of 28 metabolites in its composition, with mannitol as the major compound. AbE at 1-200 µg mL-1 and mannitol at 4-160 µg mL-1, showed low hemolytic and cytotoxic potential against human red blood cells and neutrophils. Furthermore, both were able to significantly reduce the release of myeloperoxidase. CONCLUSIONS: These results indicate that AbE is a promising natural product to be incorporated into pharmaceutical dosage forms intended for the adjuvant treatment of inflammatory diseases.
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Agaricus , Antineoplásicos , Humanos , Neutrófilos , Cromatografia Gasosa-Espectrometria de Massas , Agaricus/química , ManitolRESUMO
Cognitive deficits are already present before psychosis onset but are a key feature of first-episode psychosis (FEP). The objective of this study was to investigate the cognitive outcomes of a cohort of FEP patients who were diagnosed using the clinical staging approach and were followed for up to 21 years. We analyzed data from 173 participants with first-admission psychosis who were followed-up for a mean of 20.9 years. The clinical staging assessment was adapted from the clinical staging framework developed by McGorry et al.1 Cognitive assessment was performed using the MATRICS Consensus Cognitive Battery (MMCB) at the end of follow-up. FEP patients who were longitudinally diagnosed in the lowest clinical stages (stages 2A and 2B) showed better performance in attention, processing speed, and MCCB overall composite score than those in the highest clinical stages (stages 4A and 4B). There was a significant linear trend association between worsening of all MCCB cognitive functions and MCCB overall composite score and progression in clinical staging. Furthermore, the interval between two and five years of follow-up appears to be associated with deficits in processing speed as a cognitive marker. Our results support the validation of the clinical staging model over a long-term course of FEP based on neuropsychological performance. A decline in some cognitive functions, such as processing speed, may facilitate the transition of patients to an advanced stage during the critical period of first-episode psychosis.
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Full-thickness cutaneous trauma, due to the lack of dermis, leads to difficulty in epithelialization by keratinocytes, developing a fibrotic scar, with less elasticity than the original skin, which may have disorders in predisposed individuals, resulting in hypertrophic scar and keloids. Biomedical materials have excellent characteristics, such as good biocompatibility and low immunogenicity, which can temporarily replace traditional materials used as primary dressings. In this work, we developed two dermal matrices based on Nile tilapia collagen, with (M_GAG) and without (M) glycosaminoglycans, using a sugarcane polymer membrane as a matrix support. To assess the molecular mechanisms driving wound healing, we performed qualitative proteomic analysis on the wound bed in an in vivo study involving immunocompetent murine models at 14 and 21 days post-full-thickness skin injury. Gene Ontology and Pathway analysis revealed that both skins were markedly represented by modulation of the immune system, emphasizing controlling the acute inflammation response at 14 and 21 days post-injury. Furthermore, both groups showed significant enrichment of pathways related to RNA and protein metabolism, suggesting an increase in protein synthesis required for tissue repair and proper wound closure. Other pathways, such as keratinization and vitamin D3 metabolism, were also enriched in the groups treated with M matrix. Finally, both matrices improved wound healing in a full post-thick skin lesion. However, our preliminary molecular data reveals that the collagen-mediated healing matrix lacking glycosaminoglycan (M) exhibited a phenotype more favorable to tissue repair, making it more suitable for use before skin grafts.