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We have been encouraging practicing gynecologists to adopt molecular diagnostics tests, PCR, and cancer biomarkers, as alternatives enabled by these platforms, to traditional Papanicolaou and colposcopy tests, respectively. An aliquot of liquid-based cytology was used for the molecular test [high-risk HPV types, (HR HPV)], another for the PAP test, and one more for p16/Ki67 dual-stain cytology. A total of 4499 laboratory samples were evaluated, and we found that 25.1% of low-grade samples and 47.9% of high-grade samples after PAP testing had a negative HR HPV-PCR result. In those cases, reported as Pap-negative, 22.1% had a positive HR HPV-PCR result. Dual staining with p16/Ki67 biomarkers in samples was positive for HR HPV, and 31.7% were also positive for these markers. Out of the PCR results that were positive for any of these HR HPV subtypes, n 68.3%, we did not find evidence for the presence of cancerous cells, highlighting the importance of performing dual staining with p16/Ki67 after PCR to avoid unnecessary colposcopies. The encountered challenges are a deep-rooted social reluctance in Mexico to abandon traditional Pap smears and the opinion of many specialists. Therefore, we still believe that colposcopy continues to be a preferred procedure over the dual-staining protocol.
Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , México , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Técnicas de Diagnóstico Molecular/métodos , Teste de Papanicolaou/métodos , Biomarcadores Tumorais , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Esfregaço Vaginal , Colposcopia , Ginecologia , Adulto , Pessoa de Meia-Idade , Antígeno Ki-67/metabolismo , Antígeno Ki-67/análise , Reação em Cadeia da Polimerase/métodos , Detecção Precoce de Câncer/métodos , Prática PrivadaRESUMO
Cellular therapy has used mesenchymal stem cells (MSCs), which in cell culture are multipotent progenitors capable of producing a variety of cells limited to the mesoderm layer. There are two types of MSC sources: (1) adult MSCs, which are obtained from bone marrow, adipose tissue, peripheral blood, and dental pulp; and (2) neonatal-tissue-derived MSCs, obtained from extra-embryonic tissues such as the placenta, amnion, and umbilical cord. Until April 2023, 1120 registered clinical trials had been using MSC therapies worldwide, but there are only 12 MSC therapies that have been approved by regulatory agencies for commercialization. Nine of the twelve MSC-approved products are from Asia, with Republic of Korea being the country with the most approved therapies. In the future, MSCs will play an important role in the treatment of many diseases. However, there are many issues to deal with before their application and usage in the medical field. Some strategies have been proposed to face these problems with the hope of reaching the objective of applying these MSC therapies at optimal therapeutic levels.
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OBJECTIVE: To investigate factors associated with the nutritional status in institutionalized Mexican older adults. MATERIAL AND METHODS: In this cross-sectional study of residents in three long-term care facilities (LTCFs) in Monterrey, Mexico, a medical history, Mini-Mental State Examination, Barthel index, and geriatric depression scale, and Mini Nutritional Assessment (MNA) were performed. Risk of malnutrition and malnutrition status were defined as MNA 17-23.5 and <17, respectively. RESULTS: Residents (n = 280) had a median age of 85 years and 72.1% were female. A total of 116 (41.4%) were at risk of malnutrition and 35 (12.5%) were malnourished. Having malnutrition or being at risk of malnutrition was associated with age (OR = 1.048), functional dependence (OR = 8.376), body mass index (BMI) <22 (OR = 7.518), cognitive impairment (OR = 2.210), urinary incontinence (OR = 2.397), previous stroke (OR = 2.870), Parkinson's disease (OR = 5.193), use of calcium channel blockers (OR = 3.706), and use of atypical antipsychotics (OR = 2.277). Having benign prostatic hyperplasia (OR = 0.067) or the use of angiotensin II receptor blockers (OR = 0.038) were related to being well-nourished. CONCLUSIONS: In a population of residents of three LTCFs in Mexico, we found a high prevalence of malnutrition or being at risk of malnutrition. This underscores the need to implement guidelines for the prompt identification of this condition and further explanation of the factors identified as possibly related to malnutrition.
Assuntos
Assistência de Longa Duração , Desnutrição , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Estudos Transversais , México/epidemiologia , Desnutrição/diagnóstico , Estado Nutricional , Avaliação Nutricional , Avaliação Geriátrica , Fatores de RiscoRESUMO
The growth hormone (GH) locus has experienced a dramatic evolution in primates, becoming multigenic and diverse in anthropoids. Despite sequence information from a vast number of primate species, it has remained unclear how the multigene family was favored. We compared the structure and composition of apes' GH loci as a prerequisite to understanding their origin and possible evolutionary role. These thorough analyses of the GH loci of the chimpanzee, gorilla, and orangutan were done by resorting to previously sequenced bacterial artificial chromosomes (BACs) harboring them, as well as to their respective genome projects data available in GenBank. The GH loci of modern man, Neanderthal, gibbon, and wild boar were retrieved from GenBank. Coding regions, regulatory elements, and repetitive sequences were identified and compared among species. The GH loci of all the analyzed species are flanked by the genes CD79B (5') and ICAM-1 (3'). In man, Neanderthal, and chimpanzee, the loci were integrated by five almost indistinguishable genes; however, in the former two, they rendered three different hormones, and in the latter, four different proteins were derived. Gorilla exhibited six genes, gibbon seven, and orangutan four. The sequences of the proximal promoters, enhancers, P-elements, and a locus control region (LCR) were highly conserved. The locus evolution might have implicated duplications of the ancestral pituitary gene (GH-N) and subsequent diversification of the copies, leading to the placental single GH-V gene and the multiple CSH genes.
Assuntos
Hominidae , Hormônio do Crescimento Humano , Homem de Neandertal , Animais , Feminino , Gravidez , Hominidae/genética , Pan troglodytes/genética , Gorilla gorilla/genética , Hylobates/genética , Homem de Neandertal/genética , Sequência de Bases , Filogenia , Placenta , Hormônio do Crescimento , Hormônio do Crescimento Humano/genética , Primatas/genética , Pongo/genéticaRESUMO
Ovarian cancer (OC) represents a serious health problem worldwide. In Mexico, most OC patients are detected at late stages, consequently making OC one of the leading causes of death in women after reaching puberty. Personalized medicine (PM) provides an individualized therapeutic opportunity for treating each patient relying on "omic" tools to match the correct drug with the specific pathogenic genomic signature. PM can help predict the best therapeutic option for each affected woman suffering from OC. In recent years, Mexico has made contributions to the PM of OC; however, it still has a long way to go for its full implementation in the country's health system.
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Chronic liver diseases account for a considerable toll of incapacities, suffering, deaths, and resources of the nation's health systems. They can be prevented, treated or even cured when the diagnosis is made on time. Traditional liver biopsy remains the gold standard to diagnose liver diseases, but it has several limitations. Liquid biopsy is emerging as a superior alternative to surgical biopsy given that it surpasses the limitations: it is more convenient, readily and repeatedly accessible, safe, cheap, and provides a more detailed molecular and cellular representation of the individual patient's disease. Progress in understanding the molecular and cellular bases of diseased tissues and organs that normally release cells and cellular components into the bloodstream is catapulting liquid biopsy as a source of biomarkers for diagnosis, prognosis, and prediction of therapeutic response, thus supporting the realization of the promises of precision medicine. The review aims to summarize the evidence of the usefulness of liquid biopsy in liver diseases, including the presence of different biomarkers as circulating epithelial cells, cell-free nucleic acids, specific species of DNA and RNA, and the content of extracellular vesicles.
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Biópsia Líquida , Hepatopatias/diagnóstico , Doença Crônica , HumanosRESUMO
Abstract Background: The presence of clinically relevant mutations in KRAS and NRAS genes determines the response of anti-epidermal growth factor receptor antibody therapy for metastatic colorectal cancer (mCRC). The only quantitative polymerase chain reaction (qPCR)-based diagnostic tests approved by the Food and Drug Administration (FDA) screen merely for mutations in codons 12 and 13 of KRAS. Objective: The objective of the study was to study the frequency of clinically relevant mutations in KRAS and NRAS genes that are not included in FDA-approved qPCR tests. Methods: Formalin-fixed paraffin-embedded tumor specimens from 1113 mCRC Mexican patients from different health institutions across the country were analyzed by Sanger sequencing for KRAS mutations in exons 2, 3, and 4. Furthermore, 83 were analyzed in exons 2, 3, and 4 of NRAS. Results: From the specimens tested for KRAS, 33.69% harbored a mutation. From these, 71.77% were in codon 12 and 27.69% in codon 13 (both located in exon 2). Codons 59 (exon 3) and 146 (exon 4) accounted for the remaining 0.54%. From the 83 specimens, in which NRAS was analyzed, three mutations were found in codon 12 (3.61%). Approximately 6% of RAS mutated specimens would have been falsely reported as RAS wild type if an FDA-approved qPCR diagnostic test had been used. Conclusions: While these kits based on qPCR can be very practical and highly sensitive, their mutation coverage ignores mutations from poorly genetically characterized populations.
Assuntos
Humanos , Reação em Cadeia da Polimerase , Éxons/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , GTP Fosfo-Hidrolases/genética , Proteínas de Membrana/genética , Mutação , Kit de Reagentes para Diagnóstico , Estados Unidos , United States Food and Drug Administration , ComércioRESUMO
BACKGROUND: The presence of clinically relevant mutations in KRAS and NRAS genes determines the response of anti-epidermal growth factor receptor antibody therapy for metastatic colorectal cancer (mCRC). The only quantitative polymerase chain reaction (qPCR)-based diagnostic tests approved by the Food and Drug Administration (FDA) screen merely for mutations in codons 12 and 13 of KRAS. OBJECTIVE: The objective of the study was to study the frequency of clinically relevant mutations in KRAS and NRAS genes that are not included in FDA-approved qPCR tests. METHODS: Formalin-fixed paraffin-embedded tumor specimens from 1113 mCRC Mexican patients from different health institutions across the country were analyzed by Sanger sequencing for KRAS mutations in exons 2, 3, and 4. Furthermore, 83 were analyzed in exons 2, 3, and 4 of NRAS. RESULTS: From the specimens tested for KRAS, 33.69% harbored a mutation. From these, 71.77% were in codon 12 and 27.69% in codon 13 (both located in exon 2). Codons 59 (exon 3) and 146 (exon 4) accounted for the remaining 0.54%. From the 83 specimens, in which NRAS was analyzed, three mutations were found in codon 12 (3.61%). Approximately 6% of RAS mutated specimens would have been falsely reported as RAS wild type if an FDA-approved qPCR diagnostic test had been used. CONCLUSIONS: While these kits based on qPCR can be very practical and highly sensitive, their mutation coverage ignores mutations from poorly genetically characterized populations.
Assuntos
Éxons/genética , GTP Fosfo-Hidrolases/genética , Proteínas de Membrana/genética , Mutação , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas p21(ras)/genética , Comércio , Humanos , Kit de Reagentes para Diagnóstico , Estados Unidos , United States Food and Drug AdministrationRESUMO
Persistent high-risk human papillomavirus (HR-HPV) infections play a major role in the development of invasive cervical cancer (CC), and screening for such infections is in many countries the primary method of detecting and preventing CC. HPV typing can be used for triage and risk stratification of women with atypical squamous cells of undetermined significance (ASC-US)/low-grade cervical lesions (LSIL), though the current clinical practice in Mexico is to diagnose CC or its preceding conditions mainly via histology and HR-HPV detection. Additional information regarding these HPV infections, such as viral load and co-infecting agents, might also be useful for diagnosing, predicting, and evaluating the possible consequences of the infection and of its prevention by vaccination. The goal of this follow-up hospital case study was to determine if HPV types, multiple HPV infections, and viral loads were associated with infection persistence and the cervical lesion grade. A total of 294 cervical cytology samples drawn from patients with gynecological alterations were used in this study. HPV types were identified by real-time PCR DNA analysis. A subset of HPV-positive patients was reevaluated to identify persistent infections. We identified HPV types 16, 18, and 39 as the most prevalent. One hundred five of the patients (59%) were infected with more than one type of HPV. The types of HPV associated with multiple HPV infections were 16, 18, and 39. In the follow-up samples, 38% of patients had not cleared the initially detected HPV infection, and these were considered persistent. We found here an association between multiple HPV infections and high viral loads with and infection persistence. Our findings suggest there are benefits in ascertaining viral load and multiple HPV infections status of HR-HPV infections for predicting the risk of persistence, a requirement for developing CC. These findings contribute to our understanding of HPV epidemiology and may allow screening programs to better assess the cancer-developing risks associated with individual HR-HPV infections.