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1.
Molecules ; 29(15)2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39124967

RESUMO

The development of new methods of identification of active pharmaceutical ingredients (API) is a subject of paramount importance for research centers, the pharmaceutical industry, and law enforcement agencies. Here, a system for identifying and classifying pharmaceutical tablets containing acetaminophen (AAP) by brand has been developed. In total, 15 tablets of 11 brands for a total of 165 samples were analyzed. Mid-infrared vibrational spectroscopy with multivariate analysis was employed. Quantum cascade lasers (QCLs) were used as mid-infrared sources. IR spectra in the spectral range 980-1600 cm-1 were recorded. Five different classification methods were used. First, a spectral search through correlation indices. Second, machine learning algorithms such as principal component analysis (PCA), support vector classification (SVC), decision tree classifier (DTC), and artificial neural network (ANN) were employed to classify tablets by brands. SNV and first derivative were used as preprocessing to improve the spectral information. Precision, recall, specificity, F1-score, and accuracy were used as criteria to evaluate the best SVC, DEE, and ANN classification models obtained. The IR spectra of the tablets show characteristic vibrational signals of AAP and other APIs present. Spectral classification by spectral search and PCA showed limitations in differentiating between brands, particularly for tablets containing AAP as the only API. Machine learning models, specifically SVC, achieved high accuracy in classifying AAP tablets according to their brand, even for brands containing only AAP.


Assuntos
Acetaminofen , Aprendizado de Máquina , Análise de Componente Principal , Espectrofotometria Infravermelho , Comprimidos , Acetaminofen/química , Acetaminofen/análise , Comprimidos/química , Espectrofotometria Infravermelho/métodos , Redes Neurais de Computação , Algoritmos , Máquina de Vetores de Suporte
2.
J Immunother Cancer ; 12(7)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969523

RESUMO

BACKGROUND: Melanoma, the most lethal form of skin cancer, has undergone a transformative treatment shift with the advent of checkpoint blockade immunotherapy (CBI). Understanding the intricate network of immune cells infiltrating the tumor and orchestrating the control of melanoma cells and the response to CBI is currently of utmost importance. There is evidence underscoring the significance of tissue-resident memory (TRM) CD8 T cells and classic dendritic cell type 1 (cDC1) in cancer protection. Transcriptomic studies also support the existence of a TCF7+ (encoding TCF1) T cell as the most important for immunotherapy response, although uncertainty exists about whether there is a TCF1+TRM T cell due to evidence indicating TCF1 downregulation for tissue residency activation. METHODS: We used multiplexed immunofluorescence and spectral flow cytometry to evaluate TRM CD8 T cells and cDC1 in two melanoma patient cohorts: one immunotherapy-naive and the other receiving immunotherapy. The first cohort was divided between patients free of disease or with metastasis 2 years postdiagnosis while the second between CBI responders and non-responders. RESULTS: Our study identifies two CD8+TRM subsets, TCF1+ and TCF1-, correlating with melanoma protection. TCF1+TRM cells show heightened expression of IFN-γ and Ki67 while TCF1- TRM cells exhibit increased expression of cytotoxic molecules. In metastatic patients, TRM subsets undergo a shift in marker expression, with the TCF1- subset displaying increased expression of exhaustion markers. We observed a close spatial correlation between cDC1s and TRMs, with TCF1+TRM/cDC1 pairs enriched in the stroma and TCF1- TRM/cDC1 pairs in tumor areas. Notably, these TCF1- TRMs express cytotoxic molecules and are associated with apoptotic melanoma cells. Both TCF1+ and TCF1- TRM subsets, alongside cDC1, prove relevant to CBI response. CONCLUSIONS: Our study supports the importance of TRM CD8 T cells and cDC1 in melanoma protection while also highlighting the existence of functionally distinctive TCF1+ and TCF1- TRM subsets, both crucial for melanoma control and CBI response.


Assuntos
Linfócitos T CD8-Positivos , Fator 1-alfa Nuclear de Hepatócito , Imunoterapia , Melanoma , Humanos , Melanoma/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Imunoterapia/métodos , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Feminino , Masculino , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Idoso
3.
Sci Rep ; 14(1): 3035, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321263

RESUMO

Arterial hypertension (AH) is a multifactorial and asymptomatic disease that affects vital organs such as the kidneys and heart. Considering its prevalence and the associated severe health repercussions, hypertension has become a disease of great relevance for public health across the globe. Conventionally, the classification of an individual as hypertensive or non-hypertensive is conducted through ambulatory blood pressure monitoring over a 24-h period. Although this method provides a reliable diagnosis, it has notable limitations, such as additional costs, intolerance experienced by some patients, and interferences derived from physical activities. Moreover, some patients with significant renal impairment may not present proteinuria. Accordingly, alternative methodologies are applied for the classification of individuals as hypertensive or non-hypertensive, such as the detection of metabolites in urine samples through liquid chromatography or mass spectrometry. However, the high cost of these techniques limits their applicability for clinical use. Consequently, an alternative methodology was developed for the detection of molecular patterns in urine collected from hypertension patients. This study generated a direct discrimination model for hypertensive and non-hypertensive individuals through the amplification of Raman signals in urine samples based on gold nanoparticles and supported by chemometric techniques such as partial least squares-discriminant analysis (PLS-DA). Specifically, 162 patient urine samples were used to create a PLS-DA model. These samples included 87 urine samples from patients diagnosed with hypertension and 75 samples from non-hypertensive volunteers. In the AH group, 35 patients were diagnosed with kidney damage and were further classified into a subgroup termed (RAH). The PLS-DA model with 4 latent variables (LV) was used to classify the hypertensive patients with external validation prediction (P) sensitivity of 86.4%, P specificity of 77.8%, and P accuracy of 82.5%. This study demonstrates the ability of surface-enhanced Raman spectroscopy to differentiate between hypertensive and non-hypertensive patients through urine samples, representing a significant advance in the detection and management of AH. Additionally, the same model was then used to discriminate only patients diagnosed with renal damage and controls with a P sensitivity of 100%, P specificity of 77.8%, and P accuracy of 82.5%.


Assuntos
Hipertensão , Nefropatias , Nanopartículas Metálicas , Humanos , Análise Espectral Raman/métodos , Ouro , Monitorização Ambulatorial da Pressão Arterial , Nanopartículas Metálicas/química , Nefropatias/diagnóstico , Urinálise/métodos , Hipertensão/urina
4.
Front Oncol ; 13: 1229016, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38044992

RESUMO

Introduction: The survival of patients with metastatic renal cell carcinoma (mRCC) has improved dramatically due to novel systemic treatments. However, mRCC mortality continues to rise in Latin America. Methods: A retrospective, multicenter study of patients diagnosed with mRCC between 2010-2018 in Mexico City was conducted. The aim of the study was to evaluate the impact of healthcare insurance on access to treatment and survival in patients with mRCC. Results: Among 924 patients, 55.4%, 42.6%, and 1.9% had no insurance (NI), social security, (SS) and private insurance (PI), respectively. De novo metastatic disease was more common in NI patients (70.9%) compared to SS (47.2%) and PI (55.6%) patients (p<0.001). According to IMDC Prognostic Index, 20.2% were classified as favorable, 49% as intermediate, and 30.8% as poor-risk disease. Access to systemic treatment differed by healthcare insurance: 36.1%, 99.5%, and 100% for the NI, SS, and PI patients, respectively (p<0.001). NI patients received fewer lines of treatment, with 24.8% receiving only one line of treatment (p<0.001). Median overall survival (OS) was 13.9 months for NI, 98.9 months for SS, and 147.6 months for NI patients (p<0.001). In multivariate analysis, NI status, brain metastases, sarcomatoid features, bone metastases, no treatment were significantly associated with worse OS. Conclusion: OS in mRCC was affected by insurance availability in this resource-limited cohort of Mexican patients. These results underscore the need for effective strategies to achieve equitable healthcare access in an era of effective, yet costly systemic treatments.

5.
Environ Sci Pollut Res Int ; 30(18): 54095-54105, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36869947

RESUMO

During coal mining activities, many compounds are released into the environment that can negatively impact human health. Particulate matter, polycyclic aromatic hydrocarbons (PAHs), metals, and oxides are part of the complex mixture that can affect nearby populations. Therefore, we designed this study to evaluate the potential cytotoxic and genotoxic effects in individuals chronically exposed to coal residues from peripheral blood lymphocytes and buccal cells. We recruited 150 individuals who lived more than 20 years in La Loma-Colombia and 120 control individuals from the city of Barranquilla without a history of exposure to coal mining. In the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay, significant differences in the frequency of micronucleus (MN), nucleoplasmic bridge (NPB), nuclear bud (NBUD), and apoptotic cells (APOP) were observed between the two groups. In the buccal micronucleus cytome (BM-Cyt) assay, a significant formation of NBUD, karyorrhexis (KRX), karyolysis (KRL), condensed chromatin (CC), and binucleated (BN) cells was observed in the exposed group. Considering the characteristics of the study group, a significant correlation for CBMN-Cyt was found between NBUD and vitamin consumption, between MN or APOP and meat consumption, and between MN and age. Moreover, a significant correlation for BM-Cyt was found between KRL and vitamin consumption or age, and BN versus alcohol consumption. Using Raman spectroscopy, a significant increase in the concentration of DNA/RNA bases, creatinine, polysaccharides, and fatty acids was detected in the urine of individuals exposed to coal mining compared to the control group. These results contribute to the discussion on the effects of coal mining on nearby populations and the development of diseases due to chronic exposure to these residues.


Assuntos
Antineoplásicos , Minas de Carvão , Exposição Ocupacional , Humanos , Exposição Ocupacional/análise , Mucosa Bucal , Testes para Micronúcleos/métodos , Dano ao DNA , Linfócitos , Antineoplásicos/farmacologia
7.
J Psychosoc Oncol ; 40(6): 708-723, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34845973

RESUMO

Purpose: Identification of patients' distress is relevant for an on-time referral to psychosocial treatment. The objective was to assess the implementation of the guidelines for distress managing in Mexican oncologists based on the NCCN guidelines.Design: The study was non-experimental and cross-sectional.Sample: Two hundred thirty-one oncologists participated with an average age of 38 ± 11 years.Methods: The likelihood of distress assessment was quantitatively evaluated.Findings: A high percentage of oncologists knew and used procedures to assess psychosocial discomfort. However, a smaller percentage used a valid and reliable instrument. Factors associated with performing distress identification procedures were knowing the distress guidelines and lack of time. Factors for questionnaire usage are the availability of brief instruments and the percentage of patients suffering from stress.Implications for Psychosocial Providers: Psychosocial providers should develop strategies to educate and ensure that oncologists are familiar with guidelines on distress in oncology. More dissemination of screening procedures and referral to psychosocial programs in oncology is required. Integrating a distress screening program involving psychosocial providers and oncologists should be approached as a routine in high-quality cancer care, to reduce the stigma associated with mental health services.


Assuntos
Neoplasias , Oncologistas , Humanos , Adulto , Pessoa de Meia-Idade , Estudos Transversais , Estresse Psicológico/diagnóstico , Estresse Psicológico/psicologia , Oncologia , Neoplasias/terapia , Neoplasias/psicologia , Inquéritos e Questionários
8.
Ther Adv Chronic Dis ; 12: 20406223211047755, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34729153

RESUMO

PURPOSE: The aim of this study was to evaluate the demographic characteristics, clinical and pathological factors, and the outcome of cancer and COVID-19 patients in Mexico. PATIENTS AND METHODS: A prospective, multicentric study was performed through a digital platform to have a national registry of patients with cancer and positive SARS-CoV-2 test results through reverse transcription quantitative polymerase chain reaction (RT-qPCR). We performed the analysis through a multivariate logistic regression model and Cox proportional hazard model. RESULTS: From May to December 2020, 599 patients were registered with an average age of 56 years with 59.3% female; 27.2% had hypertension. The most frequent diagnoses were breast cancer (30.4%), lymphoma (14.7%), and colorectal cancer (14.0%); 72.1% of patients had active cancer and 23.5% of patients (141/599) were deceased, the majority of which were men (51.7%). This study found that the prognostic factors that reduced the odds of death were gender (OR = 0.42, p = 0.031) and oxygen saturation (OR = 0.90, p = 0.0001); meanwhile, poor ECOG (OR = 5.4, p = 0.0001), active disease (OR = 3.9, p = 0.041), dyspnea (OR = 2.5, p = 0.027), and nausea (OR = 4.0, p = 0.028) increased the odds of death. In the meantime, the factors that reduce survival time were age (HR = 1.36, p = 0.035), COPD (HR = 8.30, p = 0.004), having palliative treatment (HR = 10.70, p = 0.002), and active cancer without treatment (HR = 8.68, p = 0.008). CONCLUSION: Mortality in cancer patients with COVID-19 is determined by prognostic factors whose identification is necessary. In our cancer population, we have observed that being female, younger, non-COPD, with non-active cancer, good performance status, and high oxygen levels reduce the probability of death.

9.
Rev Invest Clin ; 73(6): 347-353, 2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-33053573

RESUMO

BACKGROUND: In Mexico, up to 15% of breast cancer (BC) patients are 40 years or younger. Therefore, fertility preservation and pregnancy after cancer treatment are major concerns in this population. However, no data are available regarding Mexican physicians' knowledge and attitudes toward these issues. OBJECTIVE: The objective of the study was to describe physicians' attitudes, knowledge, and perceived barriers toward fertility preservation among young women with BC (YWBC) in a developing country. METHODS: A cross-sectional study was conducted among physicians attending the 2016 Mexican Society of Oncology (SMeO) Annual Meeting or affiliated to SMeO. Chi-squared tests were used to assess factors associated with a higher likelihood of disclosing infertility risks, discussing fertility preservation methods, referring to specialists, and effective counseling. RESULTS: Of the 314 participants, 83% reported a high sense of responsibility about informing treatment-related infertility risks, 58% always informed patients about those risks, 38% always discussed fertility preservation procedures, 52% always referred interested patients to fertility specialists, and 24% wrongly considered pregnancy and GnRH analogs detrimental in YWBC. Barriers for discussing fertility preservation were costs, lack of specialists, and prognosis. CONCLUSIONS: It is crucial to promote physicians' knowledge and to endorse policies to overcome barriers obstructing universal access to fertility preservation for YWBC in Mexico.

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