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Background: CD34+ cells, megakaryocytes (MKs), and platelets express toll-like receptors (TLRs) that enable these cells to amplify the host innate immune response. However, the role of TLR7/TLR8 activation in megakaryopoiesis has not yet been investigated. Objectives: We evaluated the effect of coxsackievirus B3 (CVB3) and synthetic TLR7/TLR8 agonists on the development of human MKs and production of platelets. Methods: CD34+ cells from human umbilical cord were inoculated with CVB3 or stimulated with synthetic TLR7/TLR8 agonists and then cultured in the presence of thrombopoietin. Results: CD34+ cells, MK progenitor cells, and mature MKs expressed TLR7 and TLR8, and exposure to CVB3 resulted in productive infection, as determined by the presence of viral infectious particles in culture supernatants. Cell expansion, differentiation into MKs, MK maturation, and platelet biogenesis were significantly reduced in CD34+-infected cultures. The reduction in MK growth was not due to an alteration in cellular proliferation but was accompanied by an increase in cellular apoptosis and pyroptosis. Impairment of MK generation and maturation of viable cells were also associated with decreased expression of transcription factors involved in these processes. These effects were completely abrogated by TLR7 but not TLR8 antagonists and mimicked by TLR7 but not TLR8 agonists. CVB3 infection of CD34+ cells increased the immunophenotype of MKs characterized as CD148+/CD48+ or CD41+/CD53+ cells. Conclusion: These data suggest a novel role of TLR7 in megakaryo/thrombopoiesis that may contribute to a better understanding of the molecular basis underlying thrombocytopenia and the immunologic role of MKs in viral infection processes.
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Cervical carcinoma (CC) is the fourth most common malignancy among women. Screening with Papanicolau smear is linked to a reduction in CC incidence rates when screening programs have been developed. However, this technique has several limitations, including moderate sensitivity rates for detection of cervical preneoplastic HPV-related lesions. In this real-world study, we proposed to evaluate the sensitivity and specificity rates of cobas® test, which amplifies target DNA fragments by polymerase chain reaction and hybridization of nucleic acids for the detection of 14 HR-HPV types in a single analysis) used as primary screening test for CC and preneoplastic lesions in women aged 25-65 years in a large University Hospital in Buenos Aires. A total of 1044 patients were included in the sample (median age: 46 years); sensitivity and specificity rates for the HR-HPV test used as primary screening test were 98.66% (95% confidence interval [95CI]: 97.67-99.3%) and 87.15% (95CI: 84.93-89.15%), respectively. The positive predictive value was 88.47% (95CI: 86.54%-90.42%) and the negative predictive value was 98.48% (95CI: 97.75%-99.23%). The cobas® HR-HPV testing was highly sensitive and specific for the detection of CC and preneoplastic lesions in real practice.
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Carcinoma , Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Humanos , Feminino , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Sensibilidade e Especificidade , Programas de Rastreamento/métodos , Esfregaço Vaginal/métodos , DNA Viral/genética , DNA Viral/análise , Detecção Precoce de Câncer/métodos , Papillomaviridae/genética , Displasia do Colo do Útero/diagnósticoRESUMO
OBJECTIVES: To assess vaginal dysfunction using basic vaginal states and the presence of lactobacillary microbiota in patients with human papillomavirus (HPV) infection with no squamous intra-epithelial lesions (SIL), with low-grade squamous intra-epithelial lesions (L-SIL), and with high-grade squamous intra-epithelial lesions (H-SIL) or squamous cell carcinoma compared with a control group (HPV-negative); to establish the prevalence of bacterial vaginosis, candidiasis, and trichomoniasis in the different age groups; and to characterize the species of lactobacilli according to the type of lesion. METHODS: A cross-sectional study was carried out of patients who underwent clinical examination and collection of vaginal fornixes to study basic vaginal states and culture. Species identification of lactobacilli was performed by mass spectrometry. The results were analyzed using the χ2 and Fisher's tests; p<0.05 was considered significant. High-risk viral types were determined using a multiplex real-time polymerase chain reaction test. RESULTS: A total of 741 patients were analyzed and divided into three age groups: Group 1 aged 18-24 years (n=138), Group 2 aged 25-50 years (n=456), and Group 3 aged >50 years (n=147). All groups were further divided into an HPV-negative (control) group and an HPV-positive group without lesions, with L-SIL, or with H-SIL/squamous cell carcinoma. The prevalence of unbalanced basic vaginal states in patients with H-SIL/squamous cell carcinoma was 72.7% (p=0.03) in Group 1, 53.1% (p=0.05) in Group 2, and no cases of unbalance were detected in Group 3. The prevalence of bacterial vaginosis in women with H-SIL/squamous cell carcinoma in Group 1 was 54.5% and in Group 2 was 43.7%. Patients with H-SIL/squamous cell carcinoma had a prevalence of 21.4% of Lactobacillus crispatus, 42.9% of L. jensenii, and 14.3% of L. iners. CONCLUSIONS: A greater unbalance of vaginal microbiota was observed in patients with SIL, especially in those with H-SIL/squamous cell carcinoma. In this group, an increase in L. jensenii and L. iners compared with control was found. L. crispatus had a similar prevalence to the control group. It is important to characterize the lactobacilli species since the unbalance alters the vaginal microenvironment and acts as a co-factor in the persistence of HPV infection.
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Carcinoma de Células Escamosas , Infecções por Papillomavirus , Lesões Intraepiteliais Escamosas , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Vaginose Bacteriana , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Neoplasias do Colo do Útero/patologia , Papillomavirus Humano , Estudos Transversais , Papillomaviridae/genética , Microambiente TumoralRESUMO
Archaebacterias are considered a unique source of novel biomaterials of interest for nanomedicine. In this perspective, the effects of nanoarchaeosomes (ARC), which are nanovesicles prepared from polar lipids extracted from the extreme halophilic Halorubrum tebenquinchense, on human umbilical vein endothelial cells (HUVEC) were investigated in physiological and under inflammatory static conditions. Upon incubation, ARC (170 nm mean size, -41 mV ζ) did not affect viability, cell proliferation, and expression of intercellular adhesion molecule-1 (ICAM-1) and E-selectin under basal conditions, but reduced expression of both molecules and secretion of IL-6 induced by lypopolysaccharide (LPS), Pam3CSK4 or Escherichia coli. Such effects were not observed with TNF-α or IL-1ß stimulation. Interestingly, ARC significantly decreased basal levels of von Willebrand factor (vWF) and levels induced by all stimuli. None of these parameters was altered by liposomes of hydrogenated phosphatidylcholine and cholesterol of comparable size and concentration. Only ARC were endocytosed by HUVEC and reduced mRNA expression of ICAM-1 and vWF via NF-ĸB and ERK1/2 in LPS-stimulated cells. This is the first report of the anti-inflammatory effect of ARC on endothelial cells and our data suggest that its future use in vascular disease may hopefully be of particular interest.
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Statement of the Problem: Human papillomavirus (HPV) has a tropism for the squamous epithelium and cause a wide range of diseases, from benign lesions to invasive tumors that can affect the oral cavity. Purpose: This study aimed to estimate HPV infection in compatible stomatological lesions. Materials and Method: A cross-sectional study was carried out from March 2017 to August 2019, which included patients who attended the Oral Medicine Department of the School of Dentistry of the University of Buenos Aires who presented oral manifestations compatible with HPV infection that accepted to be studied by histopathology and determination of viral genotype by polymerase chain reaction (PCR). The study was carried out from the biopsy fixed in formalin and included in paraffin, for histopathological study and the genotypification of HPV by genotype-specific PCR and/or sequencing of the L1 fragment. To confirm the negative cases hybrid capture method was also used. The 95% OR-IC was estimated. Results: 108 patients, 76 women and 32 men were studied, who underwent a clinical stomatological examination and genotyping of HPV (PCR-specific genotype), being positive for 60 patients and negative for 48. Among the positive cases (n= 60) 46.7% (n= 28) corresponded to elevated lesions infected with high-risk HPV genotypes, 43.3% (n= 26) to elevated lesions with low-risk HPV genotypes, regarding flat lesions it was found that 5% (n=3) corresponded with high-risk HPV genotypes and another 5% (n=3) with low-risk genotypes, with OR 1,076 95% CI (0.1993-5.818). The HPV genotypes found were 2, 6, 11, 13, 16, 18, 26, 31, 32, 33, 35, 51, 58, 64 and 72. Conclusion: Our results estimated an association between white, bright, and elevated oral lesions and the presence of high-risk HPV.
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OBJECTIVES: Cervical cancer (ICC) is the fourth leading cause of mortality in women in Argentina and primary screening with conventional cytology (Papanicolaou smear) is the most widely used strategy despite its limitations. Strategies based on human papillomavirus (HPV) testing have the potential to improve detection and reduce mortality. The objective of this study is to evaluate the cost-effectiveness and budgetary impact of a strategy based on HPV testing with genotyping. METHODS: We used a decision model to compare the ICC screening strategies. The population consisted of 30- to 65-year-old females suitable for screening in Argentina. Inputs comprised epidemiologic, diagnostic performance, and costs data. The clinical impact was represented by the number of ICC detected and ICC-related mortality. Incremental cost-effectiveness ratio, estimated in terms of Argentinean pesos per life-year gained, and the budgetary impact were calculated at 5, 10, and 20 years. Univariate and probabilistic sensitivity analyses were performed. RESULTS: Primary screening with HPV testing would prevent 1853 ICC deaths and reduce mortality by 13% at year 10 compared with Papanicolaou smear. With an incremental cost-effectiveness ratio of AR$329 042 in the base case, it would be cost-effective for a cost-effectiveness threshold of 1 gross domestic product per capita. It would imply an additional expense in the first 5 years and probably savings in the subsequent ones. Sensitivity analyses confirm the robustness of the findings. CONCLUSIONS: The primary screening strategy based on HPV testing with genotyping compared with conventional cytology is most likely a cost-effective strategy in Argentina.
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Alphapapillomavirus , Papillomaviridae , Adulto , Idoso , Argentina , Análise Custo-Benefício , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genéticaRESUMO
En este trabajo se recuerdan las definiciones de salud sexual y su relación con la sexualidad. Se menciona la sexología clínica como disciplina reciente y su aporte a la promoción de la salud. Se detallan algunos trastornos sexuales que constituyen el campo de acción de la sexología clínica. Se citan estudios y estadísticas de los problemas sexuales más frecuentes. Se hace hincapié en su relación con el bienestar y la calidad de vida. Se remarca el avance científico de la sexología clínica en el siglo XXI. (AU)
In this work the definitions of sexual health and its relationship with sexuality are recalled. Clinical sexology is mentioned as a recent discipline and its contribution to health promotion. Some sexual disorders that constitute the clinical sexologys field of action are detailed. Studies and statistics of the most frequent sexual problems are cited. It emphasizes its relation to well-being and the quality of life. The scientific advance of clinical sexology in the XXI century is highlighted. (AU)
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Sexualidade/história , Sexologia/tendências , Saúde Sexual , Disfunções Sexuais Fisiológicas/diagnóstico , Disfunções Sexuais Fisiológicas/terapiaRESUMO
Se destaca la importancia de la primera consulta médica del paciente joven, que llega a la guardia médica y es recibido por un médico generalista. Es el momento ideal para realizar una medicina basada en la prevención de enfermedades orgánicas, socioculturales y psicopedagógicas que puedan comprometer la salud del adolescente. Se señalan algunos datos que el médico generalista puede obtener en esta primera entrevista sobre anomalías en el desarrollo puberal y factores de riesgo socioculturales y psicopedagógicos que pueden poner en riesgo la salud y la vida del adolescente que consulta, para realizar la posterior derivación al especialista en adolescentes.
The importance of the first medical consultation of the young patient is highlighted. It's the ideal moment to carry out a medicine based on the prevention of organic, sociocultural and psychopedagogical diseases that may compromise adolescent health. Some data that the general practitioner can obtain in this first interview about anomalies in pubertal development, sociocultural and psychopedagogical risk factors that may put at risk the health and life of the adolescent who consults and make your subsequent referral to the Teen Specialist, are point out.
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Humanos , Adolescente , Saúde do Adolescente , Prevenção de Doenças , Clínicos Gerais , Visita a Consultório Médico , Exame Físico , Relações Médico-Paciente , AnamneseRESUMO
OBJECTIVES: The aim of the study was to understand which human papillomavirus (HPV) types are involved in external genital warts (GWs) in a group of Argentinian women in Buenos Aires. METHODS: One hundred sixty consecutive women 15 to 45 years old with GWs were enrolled. All patients underwent confirmatory biopsy. In 150 of 160 patients, the diagnosis of GWs was confirmed by histology, DNA-HPV was investigated using polymerase chain reaction, and sequence analysis with generic primers MY09/11 was performed. RESULTS: HPV 6 and/or 11 was detected in 93.3% patients (140/150). HPV 6 was by far the most common type (80%), followed by HPV 11 (12.7%). Coinfection with these 2 types occurred in 0.7%. HPV 16 was found in 2% and HPV 73 in 0.7%. CONCLUSION: HPV 6 and/or 11 are present in 93.3% (95% confidence interval, 0.9-1.0) of external genital warts in a group of Argentinian women in Buenos Aires and, therefore, could be prevented with HPV vaccine (NCT 015998779).
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Condiloma Acuminado/epidemiologia , Condiloma Acuminado/virologia , Genótipo , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Adolescente , Adulto , Argentina/epidemiologia , Biópsia , DNA Viral/genética , DNA Viral/isolamento & purificação , Feminino , Histocitoquímica , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Reação em Cadeia da Polimerase , Prevalência , Análise de Sequência de DNA , Adulto JovemRESUMO
The aim of this study was to evaluate different methods for Trichomonas vaginalis diagnosis during pregnancy in order to prevent maternal and perinatal complications. A total of 386 vaginal exudates from pregnant women were analyzed. T. vaginalis was investigated by 3 types of microscopic examinations direct wet mount with physiologic saline solution, prolonged May-Grunwald Giemsa (MGG) staining, and wet mount with sodium-acetate-formalin (SAF)/methylene blue method. PCR for 18S rRNA gene as well as culture in liquid medium were performed. The sensitivity and specificity of the microscopic examinations were evaluated considering the culture media positivity or the PCR techniques as gold standard. The frequency of T. vaginalis infection was 6.2% by culture and/or PCR, 5.2% by PCR, 4.7% by culture, 3.1% by SAF/methylene blue method and 2.8% by direct wet smear and prolonged MGG staining. The sensitivities were 83.3%, 75.0%, 50.0%, and 45.8% for PCR, culture, SAF/methylene blue method, and direct wet smear-prolonged MGG staining, respectively. The specificity was 100% for all the assessed methods. Microscopic examinations showed low sensitivity, mainly in asymptomatic pregnant patients. It is necessary to improve the detection of T. vaginalis using combined methods providing higher sensitivity, such as culture and PCR, mainly in asymptomatic pregnant patients, in order to prevent maternal and perinatal complications.