RESUMO
BACKGROUND AND OBJECTIVE: Atypical nevus syndrome has been described as one of the main risk factors for melanoma. The aim of this study was to analyze dermoscopic changes observed in melanocytic lesions over a follow-up period of 5 years in patients with atypical nevus syndrome. MATERIAL AND METHODS: We conducted a retrospective follow-up study of a cohort of patients seen at a specialized skin cancer and digital body mapping clinic in Medellin, Colombia, between January 2017 and December 2022. We analyzed the dermoscopic changes observed during this period and explored their association with newly diagnosed melanoma. RESULTS: A total of 368 patients (187 women) with a median (interquartile range) age of 43 (37-51) years were included. The dermoscopic features observed at 5 years were an atypical network (222 patients, 60.3%), asymmetric globules (163, 44.2%), white-gray regression areas (105, 28.5%), lesion regression (72, 19.5%), a negative pigment network (59, 16%), asymmetric eccentric pigmentation (28, 7.6%), asymmetric projections (21, 5.7%), and asymmetric vascular patterns (8, 2.1%). Melanoma was diagnosed in 12.2% of patients during follow-up. Features significantly associated with a shorter time to melanoma onset were grayish-white areas (P <.001), asymmetric globules (P=.011), asymmetric eccentric pigmentation (P=.047), and a negative pigment network (P=.001). CONCLUSIONS: The main dermoscopic features of melanocytic lesions in patients with atypical nevus syndrome associated with progression to melanoma were grayish-white areas, asymmetric globules, asymmetric spots, and a negative pigment network.
Assuntos
Melanoma , Nevo , Neoplasias Cutâneas , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Melanoma/complicações , Melanoma/epidemiologia , Melanoma/diagnóstico , Estudos de Coortes , Estudos Retrospectivos , Seguimentos , Dermoscopia , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/diagnóstico , Nevo/diagnóstico , Nevo/patologiaRESUMO
BACKGROUND AND OBJECTIVE: Atypical nevus syndrome has been described as one of the main risk factors for melanoma. The aim of this study was to analyze dermoscopic changes observed in melanocytic lesions over a follow-up period of 5 years in patients with atypical nevus syndrome. MATERIAL AND METHODS: We conducted a retrospective follow-up study of a cohort of patients seen at a specialized skin cancer and digital body mapping clinic in Medellin, Colombia, between January 2017 and December 2022. We analyzed the dermoscopic changes observed during this period and explored their association with newly diagnosed melanoma. RESULTS: A total of 368 patients (187 women) with a median (interquartile range) age of 43 (37-51) years were included. The dermoscopic features observed at 5 years were an atypical network (222 patients, 60.3%), asymmetric globules (163, 44.2%), white-gray regression areas (105, 28.5%), lesion regression (72, 19.5%), a negative pigment network (59, 16%), asymmetric eccentric pigmentation (28, 7.6%), asymmetric projections (21, 5.7%), and asymmetric vascular patterns (8, 2.1%). Melanoma was diagnosed in 12.2% of patients during follow-up. Features significantly associated with a shorter time to melanoma onset were grayish-white areas (P<.001), asymmetric globules (P=.011), asymmetric eccentric pigmentation (P=.047), and a negative pigment network (P=.001). CONCLUSIONS: The main dermoscopic features of melanocytic lesions in patients with atypical nevus syndrome associated with progression to melanoma were grayish-white areas, asymmetric globules, asymmetric spots, and a negative pigment network.
Assuntos
Melanoma , Nevo , Neoplasias Cutâneas , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Melanoma/complicações , Melanoma/epidemiologia , Melanoma/diagnóstico , Estudos de Coortes , Estudos Retrospectivos , Seguimentos , Dermoscopia , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/diagnóstico , Nevo/diagnóstico , Nevo/patologiaRESUMO
Sulfoxaflor (Isoclast™ active) is a sulfoximine insecticide that is active on a broad range of sap-feeding insects, including species that exhibit reduced susceptibility to currently available insecticides. Colonies of Myzus persicae (green peach aphid) were established from aphids collected in the field from peach (Prunus persica) and nectarine (Prunus persica var. nucipersica) orchards in France, Italy and Spain. The presence of the nicotinic acetylcholine receptor (nAChR) point mutation R81T was determined for all the colonies. Eight of the 35 colonies collected were susceptible relative to R81T (i.e., R81T absent), three of the colonies were found to be homozygous for R81T while 24 colonies had R81T present in some proportion (heterozygous). Sulfoxaflor and imidacloprid were tested in the laboratory against these M. persicae field colonies, which exhibited a wide range of susceptibilities (sulfoxaflor RR = 0.6 to 61, imidacloprid RR = 0.7 to 986) (resistance ratios, RR) to both insecticides. Although sulfoxaflor was consistently more active than imidacloprid against these field collected M. persicae, there was a statistically significant correlation across all colonies between the RRs for imidacloprid and sulfoxaflor (Pearson's r = 0.939, p < 0.0001). However, when a larger group of the colonies from Spain possessing R81T were analyzed, there was no correlation observed for the RRs between imidacloprid and sulfoxaflor (r = 0.2901, p = 0.3604). Thus, consistent with prior studies, the presence of R81T by itself is not well correlated with altered susceptibility to sulfoxaflor. In field trials, sulfoxaflor (24 and 36 gai/ha) was highly effective (~avg. 88-96% control) against M. persicae, demonstrating similar levels of efficacy as flonicamid (60-70 gai/ha) and spirotetramat (100-180 gai/ha) at 13-15 days after application, in contrast to imidacloprid (110-190 gai/ha) and acetamiprid (50-75 gai/ha) with lower levels of efficacy (~avg. 62-67% control). Consequently, sulfoxaflor is an effective tool for use in insect pest management programs for M. persicae. However, it is recommended that sulfoxaflor be used in the context of an insecticide resistance management program as advocated by the Insecticide Resistance Action Committee involving rotation with insecticides possessing other modes of action (i.e., avoiding rotation with other Group 4 insecticides) to minimize the chances for resistance development and to extend its future utility.
Assuntos
Afídeos , Inseticidas , Receptores Nicotínicos , Animais , Afídeos/genética , Inseticidas/farmacologia , Mutação , Neonicotinoides , Nitrocompostos , Piridinas , Receptores Nicotínicos/genética , Compostos de EnxofreRESUMO
BACKGROUND: Enzyme replacement therapy (ERT) has been shown to decrease urine glycosaminoglycans (uGAGs) and liver and spleen volumes, and to improve clinical symptoms in mucopolysaccharidosis type II (MPS-II) patients. METHODS: A systematic search of the literature, from inception to August 2017, was conducted to identify randomized trials or observational studies including ≥1 MPS-II patients with ERT initiated in adult age (≥16â¯years) and evaluating ERT efficacy. Evidence was rated according to GRADE criteria. Common efficacy outcomes of the clinical studies were analyzed. Case reports were separately evaluated. RESULTS: One randomized clinical trial, 4 observational studies and 5 case reports were selected. ERT decreased uGAG levels and liver and spleen size with moderate evidence level and led to anti-ERT antibody and IRRS development in a significant proportion of patients with moderate evidence level. There were no conclusive results for beneficial effects on 6MWT, respiratory, cardiac and neurological function, joint mobility, sleep disorders of respiratory origin, and quality of life. LIMITATIONS: Excluding one observational study, all others were not conducted specifically in the target population (ERT ≥16â¯years). Data were from subgroup analyses of selected studies. There was a great heterogeneity between study designs and clinical outcomes evaluated. CONCLUSIONS: ERT improves uGAGs and liver/spleen volume with a moderate evidence level in MPS-II patients initiating therapy as adults, although the putative associated clinical benefit is unclear.
Assuntos
Terapia de Reposição de Enzimas , Iduronato Sulfatase/administração & dosagem , Mucopolissacaridose II/terapia , Adulto , Humanos , Qualidade de VidaRESUMO
We show that the critical velocity of a superfluid flow through a penetrable barrier coincides with the onset of the analog black-hole lasing effect. This dynamical instability is triggered by modes resonating in an effective cavity formed by two horizons enclosing the barrier. The location of the horizons is set by v(x)=c(x), with v(x),c(x) being the local fluid velocity and sound speed, respectively. We compute the critical velocity analytically and show that it is univocally determined by the configuration of the horizons. In the limit of broad barriers, the continuous spectrum at the origin of the Hawking-like radiation and of the Landau energetic instability is recovered.
RESUMO
PURPOSE: To improve chemotherapy protocols of lymphoid malignancies, by using polymeric and lipid microparticles as controlled delivery systems of dexamethasone, part of all combined chemotherapy protocols for its strong-inducing effect on malignant lymphoblasts. METHODS: Polymeric microparticles were prepared by the oil-in-water-emulsion cosolvent evaporation method, andlipid microparticles by spray drying. Their cytotoxic effects on GC-sensitive PC12 cells and GC-resistant PC3 cells were characterized by cell proliferation and apoptosis assays. RESULTS: Both elaboration methods rendered optimal-sized microparticles for parenteral administration with high drug loading. In vitro assays showed sustained dexamethasone release from polymeric microparticles over a month, whereas 100% dexamethasone release from lipid microparticles was achieved within 24 h. Similar PC12 cell death to that obtained with dexamethasone solution administered every 48 h was achieved with dexamethasone polymeric microparticles in 26-days assays. Dexamethasone solution and loaded polymeric microparticles induced apoptosis around 15.8 and 19.9%, respectively, after 2 days of incubation. Lipid microparticles increased further apoptosis induction in PC12 cells and, unlike dexamethasone solution and polymeric microparticles, showed antiproliferative effects on PC3 cells. CONCLUSIONS: Dexamethasone polymeric microparticles constitute an alternative to current dexamethasone administration systems in combined chemotherapy, whereas dexamethasone lipid microparticles represent a potential tool to revert glucocorticoid resistance.
Assuntos
Neoplasias das Glândulas Suprarrenais/patologia , Antineoplásicos/farmacologia , Dexametasona/farmacologia , Portadores de Fármacos , Resistencia a Medicamentos Antineoplásicos , Lipídeos/química , Feocromocitoma/patologia , Polímeros/química , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Química Farmacêutica , Dexametasona/química , Relação Dose-Resposta a Droga , Cinética , Células PC12 , Tamanho da Partícula , Ratos , Solubilidade , Tecnologia Farmacêutica/métodosRESUMO
HLA-A*03:168N differs from HLA-A*03:01:01 by a single nucleotide substitution resulting in a coding change Y27X.
Assuntos
Alelos , Antígenos HLA-A/genética , Células-Tronco Hematopoéticas/metabolismo , Teste de Histocompatibilidade , Análise de Sequência de DNA , Doadores de Tecidos , Sequência de Bases , Éxons/genética , Humanos , Masculino , Dados de Sequência Molecular , Noruega , Alinhamento de Sequência , SorotipagemRESUMO
AIM: To carry out a psychometric evaluation of the Spanish-language version of the Dundee Ready Education Environment Measure (DREEM) applied to dental students. METHODS: A total of 1,391 students from nine Spanish public schools of dentistry responded to the DREEM questionnaire. To analyse the reliability of the DREEM questionnaire, the internal consistency was assessed and a 'test-retest' carried out. Validity was evaluated through analysis of item response rate, floor and ceiling effects, corrected item-total and item-subscale correlations and factor structure. A confirmatory factor analysis was performed to analyse the structure of the original DREEM scale. RESULTS: Cronbach's alpha coefficient for the 'Educational Climate' (EC) global scale was 0.92. In the subscales, the 'observed' Cronbach's alpha coefficients ranged between 0.57 and 0.79 and were higher than the 'expected' ones; except for the Social subscale. In the DREEM questionnaire, all of the corrected correlation coefficients between the items and the EC global scale, and the items and their corresponding subscales, were >0.2; except for items 50 and 17. All goodness-of-fit indices of confirmatory factor analysis showed acceptable values (close to one or zero, depending on the case), and there was consistency in the results. CONCLUSIONS: The Spanish-language version of the DREEM questionnaire is a reliable and valid instrument for analysing the EC for dental students and its factor structure is supported by the data. Although our findings indicate that the DREEM may be as culturally independent as was originally stated, more research should be directed at verifying the factor structure in various languages and cultural environments.
Assuntos
Atitude do Pessoal de Saúde , Educação em Odontologia , Psicometria , Meio Social , Estudantes de Odontologia/psicologia , Inquéritos e Questionários , Currículo , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , EspanhaRESUMO
BACKGROUND: Recent studies have demonstrated that real-time CGM use reduce the incidence severe hypoglycemic events and impaired awareness of hypoglycemia (IAH) However, there are few real-world studies evaluating the effect of intermittently scanned continuous glucose monitoring (isCGM) on hypoglycemic episodes and hypoglycemia unawareness (IAH). The present study was designed to cover this research-practice gap. METHODS: This is a real-world, observational, prospective cohort study with 2 years of follow-up in which 60 subjects with T1D who experienced frequent hypoglycemic events were included. All the patients were invited to use isCGM type Abbott FreeStyle Libre 2® on a continuous basis for 2 years. Glucometric parameters were obtained during the initial 2 weeks using isCGM and compared with data collected for the same period at 1 year and at the end of follow-up. The IAH was evaluated using the Clarke questionnaire, and to assess psychological aspects related to hypoglycemia the Hypoglycemia Fear Survey (HFS) was used. RESULTS: After 2-years of follow-up using isCGM, we observed a decrease in glucose variability (40.3 ± 0.8 % vs. 37.1 ± 0.9 %, p = 0.003), time in low glucose range (54-69 mg/dL) (5.2 ± 0.4 % vs. 3.6 ± 0.3 %, p = 0.001), time in very low glucose range (<54 mg/dL) (3.2 ± 0.5 % vs. 0.8 ± 0.2 %, p < 0.001), less events related to low glucose levels (10.6 ± 1.1 vs 8.0 ± 1.0, p = 0.042) and a short duration of hypoglycemia episodes (106.1 ± 5.9 min vs. 85.7 ± 5.7 min, p = 0.008). In addition, participants presented a reduction of 47 % in the frequency of IAH, assessed by the Clarke questionnaire scores (24.6 % vs. 11.6 %, p = 0.034), as well as hypoglycemia fear (77.8 ± 2.4 vs 68.2 ± 2.1, p < 0.001). Furthermore, a reduction in total insulin dose was also observed (0.64 ± 0.30 UI/Kg/day vs 0.56 ± 0.11 UI/Kg/day, p = 0.018). CONCLUSIONS: In the real-world, long-term use of isCGM could reduce both hypoglycemic episodes and IAH in people with T1D.
Assuntos
Automonitorização da Glicemia , Glicemia , Diabetes Mellitus Tipo 1 , Hipoglicemia , Humanos , Hipoglicemia/sangue , Hipoglicemia/prevenção & controle , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/psicologia , Masculino , Automonitorização da Glicemia/métodos , Feminino , Estudos Prospectivos , Adulto , Glicemia/análise , Pessoa de Meia-Idade , Alarmes Clínicos , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/administração & dosagem , Seguimentos , Monitoramento Contínuo da GlicoseRESUMO
BACKGROUND: Pseudomonas aeruginosa bloodstream infections (PA-BSIs) are a serious disease and a therapeutic challenge due to increasing resistance to carbapenems. Our objectives were to describe the prevalence and risk factors associated with carbapenem resistance (CR) and mortality in children with PA-BSI. METHODS: A retrospective, multi-centre study was carried out, including patients aged <20 years with PA-BSI in four tertiary hospitals in Madrid (Spain) during 2010-2020. Risk factors for CR PA-BSIs and 30-day mortality were evaluated in a multi-variable logistic regression model. RESULTS: In total, 151 patients with PA-BSI were included, with a median age of 29 months (interquartile range: 3.5-87.1). Forty-five (29.8%) cases were CR, 9.9% multi-drug resistant and 6.6% extensively drug resistant. The prevalence of CR remained stable throughout the study period, with 26.7% (12/45) of CR mediated by VIM-type carbapenemase. Patients with BSIs produced by CR-PA were more likely to receive inappropriate empiric treatment (53.3% vs 5.7%, P<0.001) and to have been previously colonized by CR-PA (8.9% vs 0%, P=0.002) than BSIs caused by carbapenem-susceptible P. aeruginosa. CR was associated with carbapenem treatment in the previous month (adjusted odds ratio (aOR) 11.15) and solid organ transplantation (aOR 7.64). The 30-day mortality was 23.2%, which was associated with mechanical ventilation (aOR 4.24), sepsis (aOR 5.72), inappropriate empiric antibiotic therapy (aOR 5.86), and source control as a protective factor (aOR 0.16). CONCLUSION: This study shows a concerning prevalence of CR in children with PA-BSIs, leading to high mortality. Inappropriate empiric treatment and sepsis were associated with mortality. The high prevalence of CR with an increased risk of inappropriate empiric treatment should be closely monitored.
Assuntos
Bacteriemia , Carbapenêmicos , Infecções por Pseudomonas , Pseudomonas aeruginosa , Humanos , Infecções por Pseudomonas/mortalidade , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pré-Escolar , Criança , Fatores de Risco , Masculino , Feminino , Pseudomonas aeruginosa/efeitos dos fármacos , Estudos Retrospectivos , Lactente , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Adolescente , Bacteriemia/mortalidade , Bacteriemia/microbiologia , Bacteriemia/epidemiologia , Bacteriemia/tratamento farmacológico , Espanha/epidemiologia , Prevalência , Centros de Atenção Terciária/estatística & dados numéricos , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Análise de Sobrevida , Resistência beta-LactâmicaRESUMO
Peripheral nerve injury causes spontaneous and long-lasting pain, hyperalgesia, and allodynia. Excitatory amino acid receptor-dependent increases in descending facilitatory drive from the brainstem rostral ventromedial medulla (RVM) contribute to injury-evoked hypersensitivity. Although increased excitability likely reflects changes in synaptic efficacy, the cellular mechanisms underlying injury-induced synaptic plasticity are poorly understood. Neuronal pentraxin 1 (NP1), a protein with exclusive CNS expression, is implicated in synaptogenesis and AMPA receptor recruitment to immature synapses. Its role in the adult brain and in descending pain facilitation is unknown. Here, we use the spared nerve injury (SNI) model in rodents to examine this issue. We show that SNI increases RVM NP1 expression and constitutive deletion or silencing NP1 in the RVM, before or after SNI, attenuates allodynia and hyperalgesia in rats. Selective rescue of RVM NP1 expression restores behavioral hypersensitivity of knock-out mice, demonstrating a key role of RVM NP1 in the pathogenesis of neuropathic pain.
Assuntos
Proteína C-Reativa/antagonistas & inibidores , Proteína C-Reativa/fisiologia , Hiperalgesia/metabolismo , Hiperalgesia/prevenção & controle , Bulbo/metabolismo , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/fisiologia , Neuralgia/metabolismo , Neuralgia/prevenção & controle , Animais , Proteína C-Reativa/genética , Inativação Gênica/fisiologia , Hiperalgesia/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Neuralgia/genética , Neurônios/metabolismo , Manejo da Dor/métodos , Medição da Dor/métodos , Ratos , Ratos Sprague-DawleyRESUMO
AIM: To analyse the 'Educational Climate' (EC) of dental students in Spain. METHODS: The study group consisted of 1391 students from nine Spanish Public Schools of Dentistry, who responded to the questionnaire based on 'Dundee Ready Education Environment Measure' (DREEM). This questionnaire has 50 items that are grouped into five domains: Learning, Teachers, Academic, Atmosphere and Social. RESULTS: The global score on the EC was 123.1 (interpretation: 'EC more positive than negative'). The scores obtained in the different domains were: 28.0 in Learning (interpretation: 'a generally positive perception of learning'), 26.8 in Teachers (interpretation: 'teachers are going in the right direction'), 20.8 in Academic (interpretation: 'feeling more on the positive side'), 29.7 in Atmosphere (interpretation: 'a generally positive atmosphere') and 17.7 in Social (interpretation: 'social perception acceptable'). In seven items (14%), an average of <2 was detected, showing that there are some educational problem areas. Regarding the EC in the different Schools of Dentistry, an average of >100 was achieved in all of them, although there were two centres that showed significantly higher values of EC. CONCLUSIONS: Spanish dental students felt that their EC was more positive than negative and considered that the different domains were positive and acceptable. However, they pointed out the existence of several educational problem areas associated with the development of a traditional curriculum. Accordingly, and in parallel with the implementation of an innovative curriculum in all Spanish Dental Schools in the coming years, immediate educational goals must address the problem areas identified, thereby further promoting a more positive perception of EC.
Assuntos
Educação em Odontologia/estatística & dados numéricos , Faculdades de Odontologia/estatística & dados numéricos , Currículo , Docentes de Odontologia , Feminino , Humanos , Masculino , Sociologia , Espanha , Estudantes de Odontologia , Inquéritos e QuestionáriosRESUMO
Genotypic tropism testing methods are emerging as the first step before prescription of the CCR5 antagonist maraviroc (MVC) to HIV-infected patients in Europe. Studies validating genotypic tests have included other active drugs that could have potentially convoluted the effects of MVC. The maraviroc clinical test (MCT) is an in vivo drug sensitivity test based on the virological response to a short-term exposure to MVC monotherapy. Thus, our aim was to compare the results of genotypic tropism testing methods with the short-term virological response to MVC monotherapy. A virological response in the MCT was defined as a ≥ 1-log(10) decrease in HIV RNA or undetectability after 8 days of drug exposure. Seventy-three patients undergoing the MCT were included in this study. We used both standard genotypic methods (n = 73) and deep sequencing (n = 27) on MCT samples at baseline. For the standard methods, the most widely used genotypic algorithms for analyzing the V3 loop sequence, geno2pheno and PSSM, were used. For deep sequencing, the geno2pheno algorithm was used with a false-positive rate cutoff of 3.5. The discordance rates between the standard genotypic methods and the virological response were approximately 20% (including mostly patients without a virological response). Interestingly, these discordance rates were similar to that obtained from deep sequencing (18.5%). The discordance rates between the genotypic methods (tropism assays predictive of the use of the CCR5 coreceptor) and the MCT (in vivo MVC sensitivity assay) indicate that the algorithms used by genotypic methods are still not sufficiently optimized.
Assuntos
Antagonistas dos Receptores CCR5 , Cicloexanos/farmacocinética , Inibidores da Fusão de HIV/farmacocinética , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , RNA Viral/antagonistas & inibidores , Triazóis/farmacocinética , Adulto , Algoritmos , Cromatografia Líquida de Alta Pressão , Cicloexanos/sangue , Feminino , Genótipo , Inibidores da Fusão de HIV/sangue , Infecções por HIV/sangue , Infecções por HIV/virologia , HIV-1/fisiologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Maraviroc , Pessoa de Meia-Idade , Tipagem Molecular , RNA Viral/biossíntese , Receptores CCR5/metabolismo , Espectrometria de Massas em Tandem , Resultado do Tratamento , Triazóis/sangue , Carga Viral/efeitos dos fármacos , Carga Viral/genética , Tropismo Viral/efeitos dos fármacosRESUMO
Most genetic studies in colorectal carcinomas have focused on those abnormalities that are acquired by primary tumors, particularly in the transition from adenoma to carcinoma, whereas few studies have compared the genetic abnormalities of primary versus paired metastatic samples. In this study, we used high-density 500K single-nucleotide polymorphism arrays to map the overall genetic changes present in liver metastases (n=20) from untreated colorectal carcinoma patients studied at diagnosis versus their paired primary tumors (n=20). MLH1, MSH2 and MSH6 gene expression was measured in parallel by immunohistochemistry. Overall, metastatic tumors systematically contained those genetic abnormalities observed in the primary tumor sample from the same subject. However, liver metastases from many cases (up to 8 out of 20) showed acquisition of genetic aberrations that were not found in their paired primary tumors. These new metastatic aberrations mainly consisted of (1) an increased frequency of genetic lesions of chromosomes that have been associated with metastatic colorectal carcinoma (1p, 7p, 8q, 13q, 17p, 18q, 20q) and, more interestingly, (2) acquisition of new chromosomal abnormalities (eg, losses of chromosomes 4 and 10q and gains of chromosomes 5p and 6p). These genetic changes acquired by metastatic tumors may be associated with either the metastatic process and/or adaption of metastatic cells to the liver microenvironment. Further studies in larger series of patients are necessary to dissect the specific role of each of the altered genes and chromosomal regions in the metastatic spread of colorectal tumors.
Assuntos
Adenocarcinoma/genética , Adenocarcinoma/secundário , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Perfilação da Expressão Gênica/métodos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Adenocarcinoma/química , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Distribuição de Qui-Quadrado , Aberrações Cromossômicas , Neoplasias Colorretais/química , Variações do Número de Cópias de DNA , Feminino , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Hepáticas/química , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Invasividade Neoplásica , Fenótipo , Prognóstico , EspanhaRESUMO
The newly detected HLA-DPB1*136:01 is distinguished from HLA-DPB1*69:01 by a single-nucleotide exchange at position 258, resulting in a coding change 57D-->57E .
Assuntos
Cadeias beta de HLA-DP/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Substituição de Aminoácidos , Sequência de Bases , Códon , Éxons , Cadeias beta de HLA-DP/imunologia , Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade , Humanos , Íntrons , Masculino , Dados de Sequência Molecular , Sistema de Registros , Análise de Sequência de DNA , Homologia de Sequência do Ácido Nucleico , Doadores de TecidosAssuntos
Pênfigo/diagnóstico , Acantólise/etiologia , Adolescente , Epiderme/imunologia , Epiderme/patologia , Feminino , Técnica Direta de Fluorescência para Anticorpo , Humanos , Imunoglobulina G/análise , Metilprednisolona/uso terapêutico , Pênfigo/tratamento farmacológico , Pênfigo/imunologia , Pênfigo/patologia , Prurido/etiologiaRESUMO
Hypertension is the most important risk factor for global disease burden. Detection and management of hypertension are considered as key issues for individual and public health, as adequate control of blood pressure levels markedly reduces morbidity and mortality associated with hypertension. Aims of these practice guidelines for the management of arterial hypertension of the Spanish Society of Hypertension include offering simplified schemes for diagnosis and treatment for daily practice, and strategies for public health promotion. The Spanish Society of Hypertension assumes the 2018 European guidelines for management of arterial hypertension developed by the European Society of Cardiology and the European Society of Hypertension, although relevant aspects of the 2017 American College of Cardiology/American Heart Association guidelines and the 2020 International Society of Hypertension guidelines are also commented. Hypertension is defined as a persistent elevation in office systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mmHg, and assessment of out-of-office blood pressure and global cardiovascular risk are considered of key importance for evaluation and management of hypertensive patients. The target for treated blood pressure should be < 130/80 for most patients. The treatment of hypertension involves lifestyle interventions and drug therapy. Most people with hypertension need more than one antihypertensive drug for adequate control, so initial therapy with two drugs, and single pill combinations are recommended for a wide majority of hypertensive patients.
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Anti-Hipertensivos , Hipertensão , Humanos , Anti-Hipertensivos/uso terapêutico , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Determinação da Pressão ArterialRESUMO
Application of continuous positive airway pressure (CPAP) during respiratory insufficiency through a helmet interface is not well known in the Pediatric practice. The objective of this paper is to describe the necessary elements for it assembly, management and nursing care. The advantages and disadvantages of helmet compared to other interfaces are also discussed.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas/instrumentação , Insuficiência Respiratória/terapia , Doença Aguda , Criança , Desenho de Equipamento , Humanos , LactenteRESUMO
This study evaluated the health status and lifestyle habits of vulnerable, community-dwelling older adults during the first COVID-19 lockdown in Spain. A telephone assessment was carried out in 38 individuals (71% women), with a Barthel index ≥85 who were frail or had a high risk of falls. Data were compared with those from an assessment performed 9 months earlier. In the latter part of the lockdown, a high percentage of the studied individuals showed difficulties in walking up 10 steps and reported sleep problems (66%) and pain (74%). On the other hand, participants were not anxious/depressed (71%) and the majority did not report loneliness (60%). Compared to the earlier assessment, we identified a decline in functional capacity and worsening of nutritional status, but an increase in family support. Efforts should be made to implement intervention programs seeking to avoid accelerated decline under the current pandemic situation, and especially during possible new lockdowns.
Assuntos
COVID-19 , Vida Independente , Idoso , Controle de Doenças Transmissíveis , Feminino , Hábitos , Humanos , Estilo de Vida , Masculino , SARS-CoV-2 , Espanha/epidemiologiaRESUMO
ETHNO-PHARMACOLOGICAL RELEVANCE: The genus Artemisia spp. is well known for its anti-infectious properties and its high content in anti-infectious compounds, like the well-known sweet wormwood (Artemisia annua L.). Another Artemisia species, Artemisia campestris subsp. glutinosa (Besser) Batt., field wormwood, has been traditionally used as medicinal plant in the Mediterranean region. AIM OF THE STUDY: The aim of this study is to investigate the anti-HIV activity of field wormwood, to identify the compounds responsible for this activity and their structure and mechanism of action. MATERIALS AND METHODS: Antiviral activity of isolated compounds and extracts was evaluated in HIV-1 infections of lymphoblastoid cells. We also evaluated the mechanism of action of isolated compounds. Viral entry was studied comparing the inhibitory effect of isolated compounds on wild type HIV-1 and VSV pseudotyped HIV-1. To assess the viral transcriptional effect, plasmids encoding luciferase reporter genes under the control of the whole genome of HIV-1 or NF-κB or Sp1 transcription factors were transfected in the presence of the compounds under evaluation. Finally, antioxidant activity was assessed by quantitation of reduced and total glutathione in treated cell cultures. RESULTS: Ethanolic and aqueous extracts of Artemisia campestris subsp. glutinosa (Besser) Batt. subsp. glutinosa displayed anti-HIV activity in vitro, although ethanolic extract was more powerful (IC50 14.62 µg/mL). Bio-guided ethanolic extract fractionation leads to the isolation and characterization of two terpenes, damsin and canrenone, and four flavonoids, 6, 2', 4'-trimethoxyflavone, acerosin, cardamonin and xanthomicrol. All the isolated compounds inhibited HIV-1 replication in vitro with IC50 values between the middle nanomolar and the low micromolar range. Their anti-HIV mechanism of action is due to the bloking of viral entry and/or transcription inhibition, without correlation with the antioxidant activity, through interference with the cellular transcription factors NF-κB and Sp1, which are targets that are not currently reached by antiretroviral therapy. CONCLUSION: We describe here the anti-HIV activity of field wormwood, Artemisia campestris subsp. glutinosa (Besser) Batt., and the isolation and study of the mechanism of action of two terpenes and four flavonoids, responsible, at least in part, for its activity, through the inhibition of two different cellular targets affecting the HIV replication cycle. The activity of these compounds in cellular targets could explain why plant extracts can be used in the treatment of different diseases. Besides, the presence of several compounds with dual and different mechanisms of action could prove useful in the treatment of HIV-1 infection, since it could aid to overcome drug resistances and simplify drug therapy. This work is a further step in understanding the anti-infectious activity of wormwood species and their use in treating infectious diseases.