RESUMO
Arcobacter butzleri is a foodborne pathogen that mainly causes enteritis in humans, but the number of cases of bacteraemia has increased in recent years. However, there is still limited knowledge on the pathogenic mechanisms of this bacterium. To investigate how A. butzleri causes disease, single knockout mutants were constructed in the cadF, ABU_RS00335, ciaB, and flaAB genes, which might be involved in adhesion and invasion properties. These mutants and the isogenic wild-type (WT) were then tested for their ability to adhere and invade human Caco-2 and HT29-MTX cells. The adhesion and invasion of A. butzleri RM4018 strain was also visualized by a Leica CTR 6500 confocal microscope. The adhesion and invasion abilities of mutants lacking the invasion antigen CiaB or a functional flagellum were lower than those of the WTs. However, the extent of the decrease varied depending on the strain and/or cell line. Mutants lacking the fibronectin (FN)-binding protein CadF consistently exhibited reduced abilities, while the inactivation of the other studied FN-binding protein, ABU_RS00335, led to a reduction in only one of the two strains tested. Therefore, the ciaB and flaAB genes appear to be important for A. butzleri adhesion and invasion properties, while cadF appears to be indispensable.
Assuntos
Adesinas Bacterianas , Arcobacter , Aderência Bacteriana , Flagelos , Aderência Bacteriana/genética , Humanos , Arcobacter/genética , Células CACO-2 , Adesinas Bacterianas/genética , Adesinas Bacterianas/metabolismo , Flagelos/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Técnicas de Inativação de Genes , Células HT29 , Fibronectinas/metabolismo , Fibronectinas/genética , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Genes Bacterianos/genética , Células Epiteliais/microbiologia , Virulência/genéticaRESUMO
BACKGROUND: Thrombotic microangiopathy (TMA) is a rare complication after lung transplantation (LT) that has seldom been characterized in detail. Recent evidence has linked TMA other than primary atypical hemolytic uremic syndrome (aHUS) with hyperactivation of the complement alternative pathway. The focus of this investigation was to analyze the treatment response with eculizumab in TMA after LT. METHODS: Case series where we have studied 11 patients with TMA after LT from 2 Spanish tertiary healthcare centers. Clinical data and response rates to eculizumab are provided. RESULTS: The main indication for lung transplant was chronic obstructive pulmonary disease (COPD) (36%) and most cases (82%) received bilateral LT. The median time to TMA diagnosis was 11.6 months (4.7-28.9) and the TMA trigger in the majority of cases (73%) was immunosuppressive drugs. Platelet and hemoglobin nadir were 58 × 103/µL (24-108) and 7.7 g/dL (7.1-7.9), respectively. All cases presented acute kidney injury (AKI) with a median creatinine of 4 mg/dL (3.2-4.8) and 54.5% required acute dialysis. Eculizumab was started after a median time of 8 days (6-14) with a median duration of 3 weeks (2-8). Complete TMA response was observed in 7 (63.6%) cases and hematologic response in 10 (90.9%). The time to hematologic and renal response was 23 days (13-29) and 28 days (14-46), respectively. CONCLUSIONS: TMA after LT is infrequent but potentially devastating. Our findings suggest that short cycles of eculizumab may be effective for severe TMA after LT.
Assuntos
Anticorpos Monoclonais Humanizados , Inativadores do Complemento , Transplante de Pulmão , Terapia de Salvação , Microangiopatias Trombóticas , Humanos , Feminino , Masculino , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/tratamento farmacológico , Transplante de Pulmão/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Pessoa de Meia-Idade , Seguimentos , Prognóstico , Adulto , Inativadores do Complemento/uso terapêutico , Idoso , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/tratamento farmacológico , Testes de Função Renal , Sobrevivência de Enxerto/efeitos dos fármacosRESUMO
The surge in human arcobacteriosis has increased interest in determining the mechanisms involved in the pathogenesis of Arcobacter butzleri. Here, genomic analyses and in vitro Caco-2 infection, motility, urease and antimicrobial susceptibility testing (AST) assays were used to characterise the virulence and antimicrobial resistance (AMR) determinants of strains HC-1, isolated from a patient with travellers' diarrhoea, and HC-2, isolated from another with pruritus. AMR determinants conferring resistance to tetracycline (tetO, present in both genomes) and to ampicillin and amoxicillin-clavulanic acid (bla3, present in HC-2) were identified. The same determinants associated with flagellum, chemotaxis, adhesion and invasion were detected in both, but HC-1 lacked eight flagellar genes. The urease cluster was only present in HC-1. Motility and urease tests confirmed the genetic differences between strains, but no genetic marker related to the inability of HC-2 to adhere and invade was identified. This inability could be conditioning the patient's pathology.
Assuntos
Arcobacter , Humanos , Virulência/genética , Células CACO-2 , Urease , Genótipo , Fenótipo , Antibacterianos/farmacologiaRESUMO
PURPOSE OF REVIEW: Familial hypercholesterolemia is a high cardiovascular risk disorder. We will review the role of lipoprotein(a) in cardiovascular risk and in aortic valve stenosis in familial hypercholesterolemia, as well as its association with their phenotype, and strategies to identify this high-risk population. RECENT FINDINGS: Patients with familial hypercholesterolemia have higher lipoprotein(a) levels mainly due to an increased frequency of LPA variants, and the cardiovascular risk is increased twofolds when both conditions coexist. Also, an increased risk for aortic valve stenosis and valve replacement has been observed with high lipoprotein(a) levels. Assessment of lipoprotein(a) during the cascade screening for familial hypercholesterolemia is a good opportunity to identify this high-risk population. High cardiovascular risk in familial hypercholesterolemia is increased even more when lipoprotein(a) is also elevated. Measurement of lipoprotein(a) in these patients is crucial to identify those subjects who need to intensify LDL-cholesterol reduction pending availability of lipoprotein(a)-specific treatments.
Assuntos
Estenose da Valva Aórtica , Hiperlipoproteinemia Tipo II , Lipoproteína(a)/sangue , Estenose da Valva Aórtica/complicações , LDL-Colesterol , Crime , Humanos , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genéticaRESUMO
BACKGROUND: Despite most controlled trials have shown no measurable benefit of COVID-19 convalescent plasma (CCP) in patients with COVID-19, some studies suggest that early administration of CCP with high-titer anti-SARS-CoV-2 can be beneficial in selected patients. We investigated the efficacy of early administration of high-titer CCP to patients with COVID-19 who required hospitalization, STUDY DESIGN AND METHODS: Observational, propensity score (PS) matched case-control study of COVID-19 patients treated with CCP within 72 h of hospital admission and untreated controls from August 2020 to February 2021. All CCP donations had a Euroimmun anti-SARS-CoV-2 sample-to-cutoff ratio ≥3. PS matching was based on prognostic factors and presented features with high-standardized differences between the treated and control groups. The primary endpoint was mortality within 30 days of diagnosis. RESULTS: A total of 1604 patients were analyzed, 261 of whom received CCP, most (82%) within 24 h after admission. Median age was 67 years (interquartile range: 56-79), and 953 (60%) were men. Presenting factors independently associated with higher 30-day mortality were increased age, cardiac disease, hypoxemic respiratory failure, renal failure, and plasma d-dimer >700 ng/ml. After PS matching, transfusion of CCP was associated with a significant reduction in the 30-day mortality rate (odds ratio [OR]; 0.94, 95% confidence interval [CI]: 0.91-0.98; p = .001) that extended to the 60th day after COVID-19 diagnosis (OR: 0.95; 95% CI: 0.92-0.99; p = .01). CONCLUSION: Our results suggest that CCP can still be helpful in selected patients with COVID-19 and call for further studies before withdrawing CCP from the COVID-19 therapeutic armamentarium.
Assuntos
COVID-19 , Idoso , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/terapia , Teste para COVID-19 , Estudos de Casos e Controles , Feminino , Humanos , Imunização Passiva , Masculino , SARS-CoV-2 , Soroterapia para COVID-19RESUMO
AIMS: Familial hypercholesterolaemia (FH) and elevated lipoprotein(a) [Lp(a)] are inherited disorders associated with premature atherosclerotic cardiovascular disease (ASCVD). Aortic valve stenosis (AVS) is the most prevalent valvular heart disease and low-density lipoprotein cholesterol (LDL-C) and Lp(a) may be involved in its pathobiology. We investigated the frequency and predictors of severe AVS requiring aortic valve replacement (AVR) in molecularly defined patients with FH. METHODS AND RESULTS: SAFEHEART is a long-term prospective cohort study of a population with FH and non-affected relatives (NAR). We analysed the frequency and predictors of the need for AVR due to AVS in this cohort. Five thousand and twenty-two subjects were enrolled (3712 with FH; 1310 NAR). Fifty patients with FH (1.48%) and 3 NAR (0.27%) required AVR [odds ratio 5.71; 95% confidence interval (CI): 1.78-18.4; P = 0.003] after a mean follow-up of 7.48 (3.75) years. The incidence of AVR was significantly higher in patients with FH (log-rank 5.93; P = 0.015). Cox regression analysis demonstrated an association between FH and AVR (hazard ratio: 3.89; 95% CI: 1.20-12.63; P = 0.024), with older age, previous ASCVD, hypertension, increased LDL-CLp(a)-years, and elevated Lp(a) being independently predictive of an event. CONCLUSION: The need for AVR due to AVS is significantly increased in FH patients, particularly in those who are older and have previous ASCVD, hypertension, increased LDL-CLp(a)-years and elevated Lp(a). Reduction in LDL-C and Lp(a) together with control of hypertension could retard the progression of AVS in FH, but this needs testing in clinical trials.ClinicalTrials.gov number NCT02693548.
Assuntos
Hiperlipoproteinemia Tipo II , Hipertensão , Idoso , Valva Aórtica/cirurgia , LDL-Colesterol , Humanos , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Hipertensão/epidemiologia , Lipoproteína(a) , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: The gibberellins (GAs) GA5 (inhibitor of GA3 -oxidase), GA4 (biologically active), GA4/7 (commercially available mixture of Ga4 and GA7 ) prohexadione-calcium (ProCa, inhibitor of dioxygenases that render GAs bioactive, negative control), and GA3 (positive control) were applied to bunches of Vitis vinifera cv. Malbec. Different techniques, doses, and timings were used in a 3-year field experiment. In year 1, GA5 , ProCa, and GA3 were applied at 35, 20, and 0 days before veraison (DBV) by dipping bunches three times. In year 2, single applications of GA5 and GA3 , also by immersion, were tested at 60, 45, and 30 DBV. In year 3, applications at 60 and 30 DBV of GA5 , GA4 , and a mixture of GA4/7 were evaluated by dipping or spraying the bunches. RESULTS: Vegetative growth, berry weight, and sugar content were unaffected by treatments. ProCa did not affect the yield with respect to water control, although it reduced the levels of phenolics in berry skins, an undesirable effect for winemaking. GA5 , in the dose range 5-50 mg L-1 , raised berry numbers, thereby augmenting bunch weight and skin phenolics at harvest, so increasing berry quality for winemaking. GA4 and GA4/7 produced similar benefits to GA5 , with similar doses. CONCLUSION: The applications of GA5 , GA4 , and GA4/7 to developing grape berry bunches, in a range of concentrations and by dipping or spraying, increased berry numbers per bunch at harvest. The method can be used as a viticultural practice to improve the production and quality of wine grapes. © 2021 Society of Chemical Industry.
Assuntos
Vitis , Carboidratos/análise , Frutas/química , Giberelinas/farmacologia , Fenóis/análise , Vitis/químicaRESUMO
PURPOSE OF REVIEW: Degenerative aortic stenosis (AS) is one of the most prevalent heart valve diseases in the adult population. The understanding of AS pathophysiology and involved risk factors have recently undergone a great advance, with low-density lipoprotein cholesterol (LDL-C), lipoprotein (a) [Lp(a)] and other clinical conditions taking on a relevant role. Although little is known about the prevention of AS, we can progressively find more evidence of the possible use of drugs to control risk factors as tools that may delay the progression to severe AS and aortic valve replacement. RECENT FINDINGS: Several factors have shown to be solid predictors of the development of AS. Mendelian randomization and observational studies on risk factors specifically lipid factors, such as hypercholesterolemia, Lp(a), proprotein convertase subtilisin/kexin type 9 and hypertension have provided meaningful new information. The SAFEHEART study has significantly contributed to define the role of LDL-C and Lp(a) in AS. SUMMARY: In this review we discuss the interrelationship of dyslipidemia, especially hypercholesterolemia and Lp(a) in the development and prognosis of valvular AS. New imaging tools may contribute to its early detection. Future studies with proprotein convertase subtilisin/kexin type 9 inhibitors and specific therapies to lower Lp(a) might contribute to delay AS development.
Assuntos
Estenose da Valva Aórtica , Dislipidemias , Hipercolesterolemia , Adulto , Estenose da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/genética , LDL-Colesterol , Dislipidemias/complicações , Dislipidemias/genética , Humanos , Hipercolesterolemia/tratamento farmacológico , Lipoproteína(a) , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/uso terapêuticoRESUMO
This study describes the clinical presentation, treatment, and outcomes of SARS-CoV-2 infection in lung transplant recipients (LTRs). This is a multicenter, retrospective study of all adult LTRs with confirmed SARS-CoV-2 infection from March 4 until April 28, 2020 in six Spanish reference hospitals for lung transplantation. Clinical and radiological data, treatment characteristics, and outcomes were reviewed. Forty-four cases were identified in that period. The median time from transplantation was 4.2 (interquartile range: 1.11-7.3) years. Chest radiography showed acute parenchymal abnormalities in 32 (73%) cases. Hydroxychloroquine was prescribed in 41 (93%), lopinavir/ritonavir (LPV/r) in 14 (32%), and tocilizumab in 19 (43%) patients. There was a strong interaction between tacrolimus and LPV/r in all cases. Thirty-seven (84%) patients required some degree of respiratory support and/or oxygen therapy, and 13 (30%) were admitted to intermediate or intensive critical care units. Seventeen (39%) patients had died and 20 (45%) had been discharged at the time of the last follow-up. Deceased patients had a worse respiratory status and chest X-ray on admission and presented with higher D-dimer, interleukin-6, and lactate dehydrogenase levels. In this multicenter LTR cohort, SARS-CoV-2 presented with high mortality. Additionally, the severity of disease on presentation predicted subsequent mortality.
Assuntos
COVID-19/epidemiologia , Transplante de Pulmão , Transplantados , Adulto , Antivirais/uso terapêutico , COVID-19/mortalidade , Combinação de Medicamentos , Interações Medicamentosas , Humanos , Lopinavir , Pulmão , Estudos Retrospectivos , Ritonavir , SARS-CoV-2 , Espanha/epidemiologia , TacrolimoRESUMO
BACKGROUND: The use of remdesivir has demonstrated a significant reduction in the time to recovery in patients with COVID-19. However, the impact on mortality is still controversial. Therefore, it is necessary to evaluate whether there is a specific subgroup of patients in whom an active antiviral therapy also reduces the mortality. METHODS: Patients admitted for >48 h in our hospital for a SARS-CoV-2 confirmed or suspected infection from February 2020 to February 2021 were retrospectively analysed. The primary outcome of the study was mortality at 30 days. Univariate and multivariate analyses were performed to identify predictors of mortality. RESULTS: In total, 2607 patients (438 receiving remdesivir and 2169 not) were included with a median (IQR) age of 65 (54-77) years and 58% were male. Four hundred and seventy-six were admitted to the ICU (18.3%) and 264 required invasive mechanical ventilation (10.1%). The global 30 day mortality rate was 10.7%. Pre-admission symptom duration of 4-6 days and ≤3 days was associated with a 1.5- and 2.5-fold increase in the mortality rate, respectively, in comparison with >6 days and treatment with remdesivir was independently associated with a lower mortality rate (OR = 0.382, 95% CI = 0.218-0.671). The analysis showed that the major difference was among patients with shorter pre-admission symptom duration (<6 days). CONCLUSIONS: Patients with ≤3 days and 4-6 days from symptom onset to admission are associated with a 2.5- and 1.5-fold higher risk of death, respectively. Remdesivir was associated with 62% reduced odds of death versus standard-of-care and its survival benefit increased with shorter duration of symptoms.
Assuntos
Tratamento Farmacológico da COVID-19 , Monofosfato de Adenosina/análogos & derivados , Idoso , Alanina/análogos & derivados , Antivirais/uso terapêutico , Humanos , Masculino , Respiração Artificial , Estudos Retrospectivos , SARS-CoV-2RESUMO
OBJECTIVE: Characterize homozygous familial hypercholesterolemia (HoFH) individuals from Iberoamerica. Approach and Results: In a cross-sectional retrospective evaluation 134 individuals with a HoFH phenotype, 71 adults (age 39.3±15.8 years, 38.0% males), and 63 children (age 8.8±4.0 years, 50.8% males) were studied. Genetic characterization was available in 129 (96%). The majority (91%) were true homozygotes (true HoFH, n=79, 43.0% children, 46.8% males) or compound heterozygotes (compound heterozygous familial hypercholesterolemia, n=39, 51.3% children, 46.2% males) with putative pathogenic variants in the LDLR. True HoFH due to LDLR variants had higher total (P=0.015) and LDL (low-density lipoprotein)-cholesterol (P=0.008) compared with compound heterozygous familial hypercholesterolemia. Children with true HoFH (n=34) tended to be diagnosed earlier (P=0.051) and had a greater frequency of xanthomas (P=0.016) than those with compound heterozygous familial hypercholesterolemia (n=20). Previous major cardiovascular events were present in 25 (48%) of 52 children (missing information in 2 cases), and in 43 (67%) of 64 adults with LDLR variants. Children who are true HoFH had higher frequency of major cardiovascular events (P=0.02), coronary heart (P=0.013), and aortic/supra-aortic valve diseases (P=0.022) than compound heterozygous familial hypercholesterolemia. In adults, no differences were observed in major cardiovascular events according to type of LDLR variant. From 118 subjects with LDLR variants, 76 (64%) had 2 likely pathogenic or pathogenic variants. In 89 subjects with 2 LDLR variants, those with at least one null allele were younger (P=0.003) and had a greater frequency of major cardiovascular events (P=0.038) occurring at an earlier age (P=0.001). CONCLUSIONS: There was a high frequency of cardiovascular disease even in children. Phenotype and cardiovascular complications were heterogeneous and associated with the type of molecular defect.
Assuntos
Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/sangue , Homozigoto , Hiperlipoproteinemia Tipo II/genética , Mutação , Proteínas Adaptadoras de Transdução de Sinal/genética , Adolescente , Adulto , Fatores Etários , Apolipoproteína B-100/genética , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Criança , Pré-Escolar , Estudos Transversais , Europa (Continente)/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Fenótipo , Pró-Proteína Convertase 9/genética , Receptores de LDL/genética , Estudos Retrospectivos , Fatores de Risco , América do Sul/epidemiologia , Adulto JovemRESUMO
BACKGROUND AND AIMS: Familial Hypercholesterolemia (FH) is characterized by elevated LDL-cholesterol (LDL-C) and high atherosclerosis risk. The impact of different dietary patterns on atherosclerosis biomarkers has been poorly studied in FH. This study verified the association of adherence to a Mediterranean diet with biomarkers of dyslipidemia and low-grade inflammation in molecularly proven FH adults from Brazil (BR) and Spain (SP). METHODS AND RESULTS: In this cross-sectional study adherence to the Mediterranean diet was assessed by a validated score and generalized estimating equations were used to evaluate its association with plasma LDL-C, apolipoprotein-B (ApoB) and high sensitivity C-reactive protein (hs-CRP) concentrations. We included 92 (mean age 45 years, 58.7% females) and 98 FH individuals (mean age 46.8 years, 60.2% females) respectively from BR and SP. FH causing variants did not differ between countries. LDL-C, ApoB and hs-CRP concentrations were higher in BR than in SP: 179 (135-250) and 161 (133-193) mg/dL; 141 (109-181) and 103 (88-134) mg/dL; and 1.6 (0.8-4.0) and 0.8 (0.4-1.5) mg/L respectively (all p < 0.001). Most of BR had low adherence (n = 77, 83.7%), while the majority of SP were divided into moderate (n = 35, 35.7%) and strong adherence to the Mediterranean diet (n = 37, 37.8%), p < 0.001. There was a significant inverse association of adherence to the Mediterranean diet score with higher LDL-C, ApoB, and hs-CRP after adjusting for socio economic parameters, caloric and fatty acid intakes as well as pharmacological lipid lowering therapies. CONCLUSIONS: Higher adherence to a Mediterranean diet was associated with better dyslipidemia and low-grade inflammation profiles in FH.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Dieta Saudável , Dieta Mediterrânea , Hiperlipoproteinemia Tipo II/dietoterapia , Mediadores da Inflamação/sangue , Inflamação/prevenção & controle , Lipídeos/sangue , Cooperação do Paciente , Comportamento de Redução do Risco , Adulto , Biomarcadores/sangue , Brasil/epidemiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Comportamento Alimentar , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Nutritivo , Fatores de Proteção , Medição de Risco , Espanha/epidemiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
KEY MESSAGE: By studying three cv. Malbec clones cultivated in two vineyards with contrasting environmental conditions, we demonstrated that DNA methylation has an important role in the phenotypic plasticity and that epigenetic modulation is clone-dependent. Clonal selection and vegetative propagation determine low genetic variability in grapevine cultivars, although it is common to observe diverse phenotypes. Environmental signals may induce epigenetic changes altering gene expression and phenotype. The range of phenotypes that a genotype expresses in different environments is known as phenotypic plasticity. DNA methylation is the most studied epigenetic mechanism, but only few works evaluated this novel source of variability in grapevines. In the present study, we analyzed the effects on phenotypic traits and epigenome of three Vitis vinifera cv. Malbec clones cultivated in two contrasting vineyards of Mendoza, Argentina. Anonymous genome regions were analyzed using methylation-sensitive amplified polymorphism (MSAP) markers. Clone-dependent phenotypic and epigenetic variability between vineyards were found. The clone that presented the clearer MSAP differentiation between vineyards was selected and analyzed through reduced representation bisulfite sequencing. Twenty-nine differentially methylated regions between vineyards were identified and associated to genes and/or promoters. We discuss about a group of genes related to hormones homeostasis and sensing that could provide a hint of the epigenetic role in the determination of the different phenotypes observed between vineyards and conclude that DNA methylation has an important role in the phenotypic plasticity and that epigenetic modulation is clone-dependent.
Assuntos
Metilação de DNA , Polimorfismo Genético , Vitis/fisiologia , Argentina , Epigênese Genética , Fazendas , Interação Gene-Ambiente , Fenótipo , Regiões Promotoras Genéticas , Vitis/genéticaRESUMO
BACKGROUND: Most of the Chilean population has overweight or obesity. The ACTION-IO survey identified the perceptions, attitudes, and barriers to effective obesity care in people with obesity (PwO) and healthcare professionals (HCPs). AIM: To report the results of the survey in Chile. MATERIAL AND METHODS: An online survey was conducted in 11 countries. In Chile, eligible PwO were adults with a body mass index ≥ 30 kg/m2. Eligible HCPs were physicians involved in direct patient care. RESULTS: The survey was completed by 1,000 PwO and 200 HCPs in Chile. Seventy four percent of PwO and 95% of HCPs agreed that obesity was a chronic disease. Most PwO (79%) assumed responsibility for their own weight loss, while 47% of HCPs considered weight loss to be the sole responsibility of their patients. Both 82% of PwO and 97% of HCPs believed that lack of exercise was a key barrier to weight loss. Sixty six percent of PwO and 58% HCPs noted that the cost of weight management medications, programs, and services was another barrier. Compared with HCPs, more PwO felt that genetic factors prevented weight loss (26 and 44% respectively). Few HCPs (19%) thought that their patients were motivated to lose weight, while 55% of PwO reported being motivated. Most (70%) PwO had discussed their weight problem with their HCP in the past 5 years, and of those that had not, 89% want their HCP to start a discussion about weight. CONCLUSIONS: Chilean data reveal misconceptions among PwO and HCPs about obesity and highlights the need to improve education about its biologic background and clinical management.
Assuntos
Obesidade , Redução de Peso , Adulto , Chile/epidemiologia , Pessoal de Saúde , Humanos , Obesidade/epidemiologia , Obesidade/terapia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Familial hypercholesterolemia (FH) is commonly associated with mutations in-LDL receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9). AIM: To identify genetic variants associated with FH in a population of children and adolescents with hypercholesterolemia or a family history of-demonstrated early CVD. MATERIAL AND METHODS: Clinical and biochemical parameters were evaluated, and nine genes related to FH were sequenced namely LDLR, APOB, PCSK9, LDLRAP1, LIPA, APOE, ABCG5, ABCG8 and STAP1, in 55 children and adolescents aged 1 to 18 years old, from non-consanguineous families. RESULTS: Mutations associated with FH were found in 17 children and adolescents, corresponding to p.Asp47Asn, duplication of exons 13-15 and p.Ser326Cys of the LDLR gene; p.Glu204* and Ile268Met of the APOE gene. Thirteen patients were heterozygous, two homozygous, two compound heterozygous, and one double heterozygous. CONCLUSIONS: Children and adolescents carrying mutations associated with FH were found by selective screening, which constitutes the first stage in the identification of genetic variants in our country.
Assuntos
Hiperlipoproteinemia Tipo II , Pró-Proteína Convertase 9 , Adolescente , Criança , Pré-Escolar , Chile , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Lactente , Mutação , Pró-Proteína Convertase 9/genéticaRESUMO
Objective- Circulating microvesicles (cMVs) exert regulatory roles in atherothrombosis. Patients with familial hypercholesterolemia (FH) that are at high risk for premature cardiovascular events (CVEs) have previously shown high levels of cMVs related to disease severity. However, much remains unknown about their value as markers of CVE. We sought to investigate the prognostic cMV signature for future major CVE presentation in patients with FH. Approach and Results- Liquid biopsies from genetically characterized patients with FH from the SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study)-cohort without clinical manifestation of disease at entry that were going to suffer a CVE within a mean period of 3.3±2.6 years postsampling (CVE, N=92) and from age/cardiovascular risk factor/treatment-matched patients with FH that did not suffer an event within the same time-period (non-CVE, N=48) were investigated. cMVs were phenotyped by flow cytometry to identify activated parental cells. Patients with CVE had higher number of overall procoagulant annexin V+-cMVs than non-CVE ( P<0.05). Pan-leukocyte-derived and neutrophil-derived cMVs, as well as activated platelet-derived cMVs, were significantly higher in patients with CVE. Baseline number of cMVs derived from lymphocytes, neutrophils, and activated platelets were positively associated with mortality at follow-up ( P<0.05). Patient-risk calculated by classical cardiovascular risk-factor scores did not correlate with cMVs. Inclusion of the cMV signature into the SAFEHEART risk model for patients with FH for the prediction of ischemic events increased the area under the curve from 0.603±0.050 to 0.768±0.042 ( P<0.005). Conclusions- Patients with FH who are going to suffer a CVE within a mean period of 3.3 years, despite being treated according to guidelines, have ongoing innate immune cell and platelet activation. The proposed cMV signature is a prognostic marker for accelerated atherosclerosis and clinical event presentation in patients with FH.
Assuntos
Plaquetas/patologia , Isquemia Encefálica/patologia , Micropartículas Derivadas de Células/patologia , Hiperlipoproteinemia Tipo II/patologia , Leucócitos/patologia , Biópsia Líquida , Isquemia Miocárdica/patologia , Acidente Vascular Cerebral/patologia , Biomarcadores/sangue , Plaquetas/metabolismo , Isquemia Encefálica/sangue , Isquemia Encefálica/genética , Isquemia Encefálica/mortalidade , Micropartículas Derivadas de Células/metabolismo , Feminino , Predisposição Genética para Doença , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/mortalidade , Leucócitos/metabolismo , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Mutação , Isquemia Miocárdica/sangue , Isquemia Miocárdica/genética , Isquemia Miocárdica/mortalidade , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Espanha , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/mortalidade , Fatores de TempoRESUMO
Objective- Heterozygous familial hypercholesterolemia (FH) is the most common genetic disorder associated with premature atherosclerotic cardiovascular disease. Circulating microvesicles (cMV) are released when cells are activated. We investigated whether cMV could provide information on coronary calcification and atherosclerosis in FH patients. Approach and Results- Eighty-two patients (mean of 44±9 years old) with molecular diagnosis of heterozygous FH and asymptomatic cardiovascular disease were investigated. Atherosclerotic plaque characterization was performed by computed tomography angiography, and Agatston coronary calcium score and plaque composition sum were calculated. cMV were quantified by flow cytometry using AV (annexin V) and cell surface-specific antibodies. Of the 82 FH patients, 48 presented atherosclerotic plaque. Patients with atherosclerosis were men and older in a higher percentage than patients without atherosclerotic plaque. FH patients with atherosclerotic plaque showed higher levels of total AV+ cMV, cMV AV+ from platelet origin, from granulocytes and neutrophils, and cMV AV+/- from endothelial cells than FH-patients without atherosclerotic plaque. Plaque composition sum correlated with platelet- and endothelial-derived cMV, and Agatston coronary calcium score correlated with granulocyte-, platelet-, and endothelial-derived cMV. Receiver operating characteristic curve analyses indicated that the cluster of platelet-, granulocyte-, neutrophil, and endothelial-derived cMV considered together, added significant predictive value to the specific SAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study) risk equation for plaque presence (area under the curve=0.866, 95% CI, 0.775-0.958; P<0.0001, P=0.030 for the increment of the area under the curve). Conclusions- Endothelial-, granulocyte-, neutrophil- and platelet-derived cMV discriminate and map coronary atherosclerotic plaque and calcification in asymptomatic patients with FH. Liquid biopsy of cMV may be a surrogate biomarker of coronary atherosclerotic plaque burden in FH patients.
Assuntos
Doença da Artéria Coronariana/patologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/patologia , Calcificação Vascular/diagnóstico por imagem , Adulto , Área Sob a Curva , Doenças Assintomáticas , Estudos de Coortes , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico por imagem , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Biópsia Líquida , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/patologia , Prognóstico , Curva ROC , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Calcificação Vascular/patologiaRESUMO
A novel salt-tolerant alpha-proteobacterium, designated SALINAS58T, was isolated from Santa Engracia hypersaline spring water in the Añana Salt Valley, Álava, Spain. The isolate was Gram-negative, aerobic, non-motile, catalase-positive, oxidase-negative, rod-shaped and formed orange colonies on marine agar. Optimal growth was observed at pH 6.0-6.5, at 30 °C and in the presence of 1% (w/v) NaCl. The main cellular fatty acids (>20%) were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c). The major respiratory quinone was ubiquinone Q-10 and the major polar lipids detected were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidilglycerol, four unidentified glycolipids and one unidentified phospholipid. Strain SALINAS58T had the highest 16S rRNA gene sequence similarity to Altererythrobacter marensis MSW-14T (96.6%), Altererythrobacter aquaemixtae JSSK-8T (96.5%) and Pontixanthobacter luteolus SW-109T (96.5%) followed by Altererythrobacter atlanticus 26DY36T (96.4%). Results of the phylogenetic analysis, based on 16S rRNA gene sequences, and phylogenetic approaches based on whole genome nucleotide differences, showed that strain SALINAS58T could be distinguished from recognized species of the genus Altererythrobacter. The genomic DNA G+C content was 61.4 mol%. Digital DNA-DNA hybridization, average nucleotide identity and average aminoacid identity values between the genome of strain SALINAS58T and A. marensis MSW-14T were 18.4, 73.1 and 68.1%, respectively. Based on data from this polyphasic characterization, strain SALINAS58T (=CECT 30029T=LMG 31726T) is considered to be classified as representing a novel species in the genus Altererythrobacter, for which the name Altererythrobacter muriae sp. nov. is proposed.
RESUMO
OBJECTIVE: Healthy lifestyle habits are the cornerstone in the management of familial hypercholesterolaemia (FH). Nevertheless, dietary studies on FH-affected populations are scarce. The present study analyses dietary habits, adherence to a Mediterranean diet pattern and physical activity in an adult population with FH and compares them with their non-affected relatives. DESIGN: Cross-sectional study. SETTING: Data came from SAFEHEART, a nationwide study in Spain.ParticipantsIndividuals (n 3714) aged ≥18 years with a genetic diagnosis of FH (n2736) and their non-affected relatives (n 978). Food consumption was evaluated using a validated FFQ. RESULTS: Total energy intake was lower in FH patients v. non-affected relatives (P<0·005). Percentage of energy from fats was also lower in the FH population (35 % in men, 36 % in women) v. those non-affected (38 % in both sexes, P<0·005), due to the lower consumption of saturated fats (12·1 % in FH patients, 13·2 % in non-affected, P<0·005). Consumption of sugars was lower in FH patients v. non-affected relatives (P<0·05). Consumption of vegetables, fish and skimmed milk was higher in the FH population (P<0·005). Patients with FH showed greater adherence to a Mediterranean diet pattern v. non-affected relatives (P<0·005). Active smoking was lower and moderate physical activity was higher in people with FH, especially women (P<0·005). CONCLUSIONS: Adult patients with FH report healthier lifestyles than their non-affected family members. They eat a healthier diet, perform more physical activity and smoke less. However, this patient group's consumption of saturated fats and sugars still exceeds guidelines.
Assuntos
Dieta Mediterrânea/psicologia , Família/psicologia , Comportamento Alimentar/psicologia , Estilo de Vida Saudável , Hiperlipoproteinemia Tipo II/psicologia , Adulto , Estudos Transversais , Inquéritos sobre Dietas , Exercício Físico/psicologia , Feminino , Humanos , Hiperlipoproteinemia Tipo II/terapia , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/psicologia , Cooperação do Paciente/estatística & dados numéricosRESUMO
BACKGROUND: Ablative fractional laser surgery is a common technique for treating acne scars. However, an in vivo and noninvasive analysis of the histologic variations between acne skin and the resulting resurfaced skin is needed in order to evaluate the wound healing process of the scars induced by the ablative fractional laser surgery. MATERIALS AND METHODS: Nine patients with acne scars underwent a single treatment with a CO2 ablative fractional laser surgery. Collagen presence on the resurfaced skin was noninvasively assessed by means of Raman spectroscopy and principal component analysis. RESULTS: Principal component analysis shows that all the patients presented a collagen regeneration on the resurfaced skin after the laser treatment. CONCLUSION: Collagen plays a crucial role in the wound healing process. By assessing the collagen presence on the skin, it was possible to quantify the regenerative effects of the ablative fractional laser in a noninvasive way.