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1.
Int J Mol Sci ; 25(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474052

RESUMO

Juvenile Idiopathic Arthritis (JIA) is currently the most common chronic rheumatic disease in children. It is known to have no single identity, but a variety of diagnoses. Under-diagnosis is a barrier to early treatment and reduced complications of the disease. Other immune-mediated diseases may coexist in the same patient, making research in this area relevant. The main objective was to analyse whether links could be established between the molecular basis of JIA and other immune-mediated diseases. Early diagnosis may benefit patients with JIA, which in most cases goes undetected, leading to under-diagnosis, which can have a negative impact on children affected by the disease as they grow up. METHODS: We performed a PRISMA systematic review focusing on immune molecules present in different autoimmune diseases. RESULTS: A total of 13 papers from different countries dealing with the molecular basis of JIA and other immune diseases were evaluated and reviewed. CONCLUSIONS: Most of the autoimmune diseases analysed responded to the same group of drugs. Unfortunately, the reason for the under-diagnosis of these diseases remains unknown, as no evidence has been found to correlate the immunomolecular basis with the under-diagnosis of these immune-mediated diseases. The lack of information in this area means that further research is needed in order to provide a sound basis for preventing the development of immune-mediated diseases, especially in children, and to improve their quality of life through early diagnosis and treatment.

2.
Reprod Biomed Online ; 46(2): 371-378, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36428176

RESUMO

RESEARCH QUESTION: Is a low platelet count related to an increased risk of severe disease in pregnant women with active severe acute respiratory syndrome coronavirus 2 infection? DESIGN: A cross-sectional multicentre study in pregnant women with COVID-19 confirmed by polymerase chain reaction, antigen test, antibody test, or all. RESULTS: A total of 153 pregnant women with COVID-19 were included in the study, of whom 12.4% had thrombocytopaenia. Pregnant women with thrombocytopaenia were on average 3.1 years older (95% CI 0.18 to 6.38) than women without thrombocytopaenia. Pregnant smokers had a higher risk of thrombocytopaenia than non-smokers (OR 6.55, CI 95% 1.29 to 33.13). B Rh negative (B Rh-) pregnant women had a much higher risk of thrombocytopaenia than pregnant women with other blood groups (OR 16.83, CI 95% 1.42 to 199.8). Pregnant women with thrombocytopaenia had a much higher risk of suffering from preeclampsia (OR 16.2, CI 95% 1.35 to 193.4). CONCLUSIONS: COVID-19 infection is not a risk factor for a low platelet count in pregnant women, although the risk is increased by smoking and in women with blood group B Rh-. In case of pregnancy with thrombocytopaenia, COVID-19 infection leads to an increased risk of preeclampsia.


Assuntos
COVID-19 , Pré-Eclâmpsia , Complicações Infecciosas na Gravidez , Trombocitopenia , Gravidez , Feminino , Humanos , COVID-19/complicações , Pré-Eclâmpsia/epidemiologia , Estudos Transversais , Trombocitopenia/complicações
3.
Eur J Pediatr ; 182(1): 213-223, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36282323

RESUMO

Giardia duodenalis, Cryptosporidium spp., and Blastocystis sp. are common intestinal eukaryotic parasites affecting children in developed and resource-limited countries. Lack of information on the epidemiology and long-term stability in asymptomatic children complicates interpretation of transmission and pathogenesis. To assess the occurrence, genetic diversity, and temporal dynamics of intestinal eukaryotic parasites in young children, 679 stool samples from 125 toddlers attending six public day-care centres in Central Spain were collected bimonthly within a 1-year period. Detection and identification of species/genotypes were based on PCR and Sanger sequencing methods. Four eukaryotic species were identified: G. duodenalis (2.5‒31.6%), Cryptosporidium spp. (0.0‒2.4%), Blastocystis sp. (2.5‒6.4%), and Entamoeba dispar (0.0‒0.9%). Entamoeba histolytica and Enterocytozoon bieneusi were undetected. Sequence analyses identified assemblage A (63.6%) and B (36.4%) within G. duodenalis (n = 11), C. hominis (40%), C. parvum (40%), and C. wrairi (20%) within Cryptosporidium spp. (n = 5), and ST1 (3.8%), ST2 (46.2%), ST3 (15.4%), and ST4 (34.6%) within Blastocystis sp. (n = 26). Giardia duodenalis sub-assemblage AII/AIII was detected in a toddler for 10 consecutive months. Stable carriage of Blastocystis ST2 allele 9, ST3 allele 34, and ST4 allele 42 was demonstrated in five toddlers for up to 1 year.   Conclusions: Giardia duodenalis and Blastocystis sp. were common in toddlers attending day-care centres in Central Spain. Long-term infection/colonization periods by the same genetic variant were observed for G. duodenalis (up to 10 months) and Blastocystis sp. (up to 12 months). What is Known: • Asymptomatic carriage of G. duodenalis and Blastocystis sp. is frequent in toddlers. • The epidemiology and long-term stability of these eukaryotes in asymptomatic young children is poorly understood. What is New: • Long-term colonization/infection periods by the same genetic variant were described for Blastocystis sp. (up to 12 months) and G. duodenalis (up to 10 months).


Assuntos
Blastocystis , Criptosporidiose , Cryptosporidium , Giardia lamblia , Giardíase , Enteropatias Parasitárias , Humanos , Pré-Escolar , Giardia lamblia/genética , Blastocystis/genética , Giardíase/epidemiologia , Giardíase/parasitologia , Criptosporidiose/epidemiologia , Criptosporidiose/parasitologia , Prevalência , Espanha/epidemiologia , Estudos Longitudinais , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Cryptosporidium/genética , Enteropatias Parasitárias/epidemiologia , Enteropatias Parasitárias/parasitologia , Fezes/parasitologia , Genótipo
4.
Parasitol Res ; 121(10): 3007-3011, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35906999

RESUMO

Cryptosporidiosis is a leading cause of childhood diarrhoea. Two species, Cryptosporidium hominis and Cryptosporidium parvum, are responsible for most confirmed cases globally. Close contact with pet animals can be an unnoticed source of children infections. We describe a case of infection by rodent-adapted Cryptosporidium wrairi in a 22-month-old immunocompetent toddler with no clinical manifestations in close contact with a pet guinea pig and poor personal hygiene practices in Majadahonda (Madrid, Spain). Attempts to determine the C. wrairi genotype family at the 60-kDa glycoprotein marker failed repeatedly. This is the first description of C. wrairi in a human host. Although a spurious infection cannot be completely ruled out, data presented here suggest that C. wrairi can be transmitted zoonotically.


Assuntos
Criptosporidiose , Cryptosporidium parvum , Cryptosporidium , Animais , Criptosporidiose/diagnóstico , Cryptosporidium/genética , Cryptosporidium parvum/genética , Fezes , Genótipo , Cobaias , Humanos , Lactente , Roedores , Espanha
5.
Tohoku J Exp Med ; 252(3): 185-191, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33087636

RESUMO

Iodine deficiency in Spain is a persisting public health problem and the prescription of potassium iodide is recommended during pregnancy. The purpose of this study was to develop an Artificial Neural Network (ANN) to predict the risk factors of iodine deficiency during pregnancy, and compare the results obtained with a logistic regression model. Two hundred forty-four healthy pregnant women were included in a descriptive and prospective study in their first trimester of pregnancy. The women enrolled were asked specifically about their use of supplements containing potassium iodide, iron, folic acid and/or multivitamins during pregnancy. The consumption of iodine-rich foods was assessed through a food frequency questionnaire. A median UIC of 57.4 µg/L (IQR 32.8-99.3) was obtained, with 89.3% < 150 µg/L, the minimum recommended ioduria level by the WHO. There was no correlation between urinary iodine concentrations and maternal age, BMI or gestation week at recruitment. The urinary iodine concentrations were significantly higher in women who reported taking iodized supplements and/or iodized salt than those who did not. Number of gestations, age, body mass index, and intake of iodized supplements and iodized salt were the most important predictors of iodine deficiency. Based on Receiver Operating Characteristic analysis, the diagnostic performance of the ANN model was superior to the logistic regression model. The ANN model, with variables on pregnancy and the intake of iodine rich foods, iodized supplement and iodized salt may be useful for predicting iodine deficiency in the early pregnancy.


Assuntos
Comportamento Alimentar , Iodo/deficiência , Estado Nutricional , Primeiro Trimestre da Gravidez/sangue , Adolescente , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Ácido Fólico/análise , Alimentos , Humanos , Iodo/urina , Ferro/análise , Idade Materna , Redes Neurais de Computação , Gravidez , Estudos Prospectivos , Curva ROC , Análise de Regressão , Espanha , Inquéritos e Questionários , Adulto Jovem
6.
BMC Geriatr ; 19(1): 101, 2019 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-30971215

RESUMO

BACKGROUND: Previous observational studies and clinical trials have shown that cholinesterase inhibitors (with or without memantine) provide benefit for patients with mild-to-moderate Alzheimer's disease. However, the impact of treatment continuation after progression to severe disease is unknown. The main aim of this study is to evaluate the effect and safety of continuing treatment with ChEIs (with or without memantine) for patients with severe dementia. METHODS: This randomized, pragmatic, open-label clinical trial with blinded evaluators will evaluate the efficacy of continuing drug treatment in patients with advanced dementia. A total of 302 community-dwelling patients with severe dementia, Alzheimer's disease, with or without a coexisting diagnosis of vascular dementia, and a score of 10 or less on the Mini-Mental State Examination who received previous treatment with a cholinesterase inhibitor (with or without memantine) for at least 3 months, will be randomized to continue or discontinue drug treatment. Follow-up will be 12 months or until the primary endpoint is achieved. The primary endpoint is entry into institutional care and progression of disability, defined as a loss of 2 of 4 basic functions, or 6 of 11 instrumental functions, according to the Bristol Activities of Daily Living Scale at 12 months. The secondary outcomes are patient changes in functional and cognitive state, quality of life, and caregiver burden. DISCUSSION: We expect that the results of our study will allow to identify if there is clinical relevant impact for patients and caregivers between maintaining or halting pharmacological treatment. TRIAL REGISTRATION: The study was prospectively registered in the REec (2017-000042-22) on May 11 2017 and ID ISRCTN12134230 on February 25 2019.


Assuntos
Demência/tratamento farmacológico , Demência/psicologia , Índice de Gravidade de Doença , Suspensão de Tratamento/tendências , Atividades Cotidianas/psicologia , Idoso , Idoso de 80 Anos ou mais , Inibidores da Colinesterase/uso terapêutico , Demência/diagnóstico , Feminino , Humanos , Masculino , Memantina , Qualidade de Vida/psicologia , Método Simples-Cego , Resultado do Tratamento
7.
J Geriatr Psychiatry Neurol ; 31(4): 177-185, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29966477

RESUMO

OBJECTIVES: To assess the prevalence of neuropsychiatric symptoms (NPS) in mild-to-moderate Alzheimer disease (AD) and their association with caregiver burden. METHODS: Secondary analyses of baseline data from the Trial of Vitamin E and Memantine in Alzheimer's Disease (TEAM-AD) (N=613). Neuropsychiatric Inventory were used to measure severity of NPS and caregiver activity survey to measure caregiver burden. RESULTS: A total of 87% of patients displayed at least 1 NPS; 70% displayed clinically meaningful NPS. The most common symptoms were apathy (47%), irritability (44%), agitation (42%), and depression (40%). Those with moderate AD had more severe NPS than those with mild AD ( P = .03). Neuropsychiatric symptoms were significantly associated with caregiver time after adjusting for age, education, cognitive function, and comorbidity ( P-value < .0001) with every point increase in NPS associated with a 10-minute increase in caregiver time. CONCLUSION: Neuropsychiatric symptoms were prevalent in both mild and moderate AD, even in patients receiving treatment with an acetylcholinesterase inhibitors, and were more severe in moderate AD and associated with greater caregiver time.


Assuntos
Doença de Alzheimer/complicações , Cuidadores/psicologia , Testes Neuropsicológicos/normas , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Feminino , Humanos , Masculino
8.
Lancet Oncol ; 18(5): 672-681a, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28389316

RESUMO

BACKGROUND: Maintenance therapy improves outcomes in various tumour types, but cumulative toxic effects limit the choice of drugs. We investigated whether maintenance therapy with vinflunine would delay disease progression in patients with advanced urothelial carcinoma who had achieved disease control with first-line chemotherapy. METHODS: We did a randomised, controlled, open-label, phase 2 trial in 21 Spanish hospitals. Eligible patients had locally advanced, surgically unresectable, or metastatic transitional-cell carcinoma of the urothelial tract, adequate organ function, and disease control after four to six cycles of cisplatin and gemcitabine (carboplatin allowed after cycle four). Patients were randomly assigned (1:1) to receive vinflunine or best supportive care until disease progression. We initially used block randomisation with a block size of six. Four lists were created for the two stratification factors of starting dose of vinflunine and presence of liver metastases. After a protocol amendment, number of cisplatin and gemcitabine cycles was added as a stratification factor, and eight lists were created, still with a block size of six. Finally, we changed to a minimisation procedure to reduce the risk of imbalance between groups. Vinflunine was given every 21 days as a 20 min intravenous infusion at 320 mg/m2 or at 280 mg/m2 in patients with an Eastern Cooperative Oncology Group performance status score of 1, age 75 years or older, previous pelvic radiotherapy, or creatinine clearance lower than 60 mL/min. The primary endpoint was median progression-free survival longer than 5·3 months in the vinflunine group, assessed by modified intention to treat. Comparison of progression-free survival between treatment groups was a secondary endpoint. This trial is registered with ClinicalTrials.gov, number NCT01529411. FINDINGS: Between April 12, 2012, and Jan 29, 2015, we enrolled 88 patients, of whom 45 were assigned to receive vinflunine and 43 to receive best supportive care. One patient from the vinflunine group was lost to follow-up immediately after randomisation and was excluded from the analyses. One patient in the best supportive care group became ineligible for the study and did not receive treatment due to a delay in enrolment, but was included in the intention-to-treat efficacy analysis. After a median follow-up of 15·6 months (IQR 8·5-26·0), 29 (66%) of 44 patients in the vinflunine group had disease progression and 24 (55%) had died, compared with 36 (84%) of 43 patients with disease progression and 32 (74%) deaths in the best supportive care group. Median progression-free survival was 6·5 months (95% CI 2·0-11·1) in the vinflunine group and 4·2 months (2·1-6·3) in the best supportive care group (hazard ratio 0·59, 95% CI 0·37-0·96, p=0·031). The most common grade 3 or 4 adverse events were neutropenia (eight [18%] of 44 in the vinflunine group vs none of 42 in the best supportive care group), asthenia or fatigue (seven [16%] vs one [2%]), and constipation (six [14%] vs none). 18 serious adverse events were reported in the vinflunine group and 14 in the best supportive care group. One patient in the vinflunine group died from pneumonia that was deemed to be treatment related. INTERPRETATION: In patients with disease control after first-line chemotherapy, progression-free survival exceeded the acceptable threshold with vinflunine maintenance therapy. Moreover, progression-free survival was longer with vinflunine maintenance therapy than with best supportive care. Vinflunine maintenance had an acceptable safety profile. Further studies of the role of vinflunine are warranted. FUNDING: Pierre-Fabre Médicament.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Quimioterapia de Manutenção , Neoplasias Urológicas/tratamento farmacológico , Vimblastina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Astenia/induzido quimicamente , Carboplatina/administração & dosagem , Carcinoma de Células de Transição/secundário , Cisplatino/administração & dosagem , Constipação Intestinal/induzido quimicamente , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Progressão da Doença , Intervalo Livre de Doença , Fadiga/induzido quimicamente , Feminino , Seguimentos , Humanos , Análise de Intenção de Tratamento , Quimioterapia de Manutenção/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neoplasias Urológicas/patologia , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico , Gencitabina
9.
Emerg Infect Dis ; 23(8): 1431-1433, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28726627

RESUMO

We identified the mucus-activatable Shiga toxin genotype stx2d in the most common hemolytic uremic syndrome-associated Escherichia coli serotype, O157:H7. stx2d was detected in a strain isolated from a 2-year-old boy with bloody diarrhea in Spain, and whole-genome sequencing was used to confirm and fully characterize the strain.


Assuntos
Infecções por Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Escherichia coli O157/classificação , Escherichia coli O157/genética , Genótipo , Muco/metabolismo , Toxina Shiga/genética , Pré-Escolar , Escherichia coli O157/patogenicidade , Genoma Bacteriano , Síndrome Hemolítico-Urêmica/metabolismo , Síndrome Hemolítico-Urêmica/microbiologia , Humanos , Masculino , Sorogrupo , Espanha , Fatores de Virulência/genética
10.
Am J Geriatr Psychiatry ; 24(9): 675-89, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27396668

RESUMO

OBJECTIVE: The Accreditation Council of Graduate Medical Education (ACGME) Milestone Project is the next step in a series of changes revamping the system of graduate medical education. In 2013 the ACGME completed the general psychiatry milestones. The ACGME then pursued creation of milestones for accredited psychiatric subspecialty fellowships. This article documents the work of the geriatric psychiatry subspecialty milestones work group. It reports the history and rationale supporting the milestones, the milestone development process, and the implications for geriatric psychiatry fellowship training. METHODS: In consultation with the American Association for Geriatric Psychiatry, the American Board of Psychiatry and Neurology, and the ACGME Psychiatry Residency Review Committee, the ACGME appointed a working group to create the geriatric psychiatry milestones using the general psychiatry milestones as a guide. CONCLUSION: The geriatric psychiatry milestones are the result of an iterative process resulting in the definition of the characteristics vital to a fellowship-trained geriatric psychiatrist. It is premature to assess their effect on psychiatric training. The true impact of the milestones will be determined as each training director uses the milestones to re-evaluate their program curriculum and the educational and clinical learning environment. The ACGME is currently collecting the information about the milestone performance of residents and fellows to further refine and determine how the milestones can best be used to assist programs in improving training.


Assuntos
Educação de Pós-Graduação em Medicina/organização & administração , Educação , Bolsas de Estudo , Psiquiatria Geriátrica/educação , Acreditação , Competência Clínica/normas , Currículo/normas , Educação/métodos , Educação/normas , Bolsas de Estudo/métodos , Bolsas de Estudo/organização & administração , Humanos , Avaliação das Necessidades , Melhoria de Qualidade , Estados Unidos
11.
BMC Endocr Disord ; 15: 78, 2015 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-26637348

RESUMO

BACKGROUND: The main purpose of the present study is to evaluate whether treatment with long-acting human glucagon-like peptide-1 liraglutide was associated with an improvement of excessive daytime sleepiness (EDS) in obese subjects with type-2 diabetes. METHODS: This single-centre retrospective study included 158 obese (body mass index [BMI] ≥ 30 kg/m(2)) adult subjects with type-2 diabetes who were initiated with liraglutide treatment at least 3 months before study inclusion. Data of the Epworth Sleepiness Scale (ESS), anthropometric parameters, glucose-control and metabolic parameters were collected at liraglutide initiation (baseline) and at months 1 and 3 after liraglutide initiation. RESULTS: Significant reductions in ESS score were achieved at months 1 (-1.3 ± 2.8, p < 0.001) and 3 (-1.5 ± 3.0, p < 0.001) after liraglutide introduction. After 3 months of treatment with liraglutide, significant changes in body weight (p < 0.001), BMI (p < 0.001), waist (p < 0.001) and neck circumferences (p < 0.005), HbA1c (p < 0.001), mean blood glucose (p < 0.001), fasting plasma glucose (p < 0.001), triglycerides (p < 0.01) and total cholesterol (p < 0.001) were achieved. CONCLUSIONS: After 3 months of treatment with liraglutide a significant reduction in EDS was observed in obese subjects with type-2 diabetes. Besides this, significant changes in body weight and metabolic parameters of diabetes control were also accomplished. Further investigation is required to determine whether liraglutide could improve other abnormal sleep patterns and obstructive sleep apnoea.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Distúrbios do Sono por Sonolência Excessiva/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Liraglutida/uso terapêutico , Obesidade/fisiopatologia , Glicemia/efeitos dos fármacos , Índice de Massa Corporal , Colesterol , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Distúrbios do Sono por Sonolência Excessiva/etiologia , Distúrbios do Sono por Sonolência Excessiva/fisiopatologia , Feminino , Peptídeo 1 Semelhante ao Glucagon/efeitos dos fármacos , Hemoglobinas Glicadas/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Estudos Retrospectivos , Espanha/epidemiologia , Resultado do Tratamento
14.
Am J Geriatr Psychiatry ; 22(1): 86-97, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24314889

RESUMO

OBJECTIVES: Examine the longitudinal course of posttraumatic stress disorder (PTSD) in older adults and its influence on mental health quality of life (MHQoL). DESIGN: Evaluation performed at baseline, and 3 and 6 months postrandomization as part of a longitudinal trial. PARTICIPANTS AND SETTINGS: A total of 1,185 participants, with a mean (±SD) age of 73.53 (±5.98) years, at seven primary care sites (including five Veterans Affairs clinics), were divided into four groups, namely, no trauma (n = 661), trauma only (n = 319), partial PTSD (n = 114), and PTSD (n = 81), based on reports of trauma and associated PTSD symptoms. MEASUREMENTS: The prevalence of comorbid depression, anxiety, and alcohol use disorders, assessed using the Diagnostic and Statistical Manual, Fourth Edition, criteria and changes in MHQoL, as assessed by the Short Form-36 mental component score. RESULTS: At baseline, the PTSD group had higher frequencies of comorbid depression and anxiety disorders and worse MHQoL than the other groups. Both chronic (participants diagnosed with PTSD at all three assessments) and fluctuating (participants moving to or from one of the other groups) trajectories of course were observed during the follow-up period, which appeared to be separate from that of the comorbid disorders. Even after accounting for those comorbid disorders, PTSD had an independent association with poorer MHQoL at multiple time points, especially in men, whereas trauma without PTSD symptoms (trauma only) had better MHQoL. CONCLUSIONS: PTSD had chronic and fluctuating courses, with negative effects on MHQoL, while partial PTSD might represent a transitional state, underscoring the need to better identify and treat PTSD at any phase in later life.


Assuntos
Envelhecimento/psicologia , Qualidade de Vida/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Idoso , Transtornos Relacionados ao Uso de Álcool/epidemiologia , Ansiedade/epidemiologia , Doença Crônica/epidemiologia , Doença Crônica/psicologia , Comorbidade , Depressão/epidemiologia , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Estados Unidos/epidemiologia , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/psicologia
15.
JAMA ; 311(1): 33-44, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24381967

RESUMO

IMPORTANCE: Although vitamin E and memantine have been shown to have beneficial effects in moderately severe Alzheimer disease (AD), evidence is limited in mild to moderate AD. OBJECTIVE: To determine if vitamin E (alpha tocopherol), memantine, or both slow progression of mild to moderate AD in patients taking an acetylcholinesterase inhibitor. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled, parallel-group, randomized clinical trial involving 613 patients with mild to moderate AD initiated in August 2007 and concluded in September 2012 at 14 Veterans Affairs medical centers. INTERVENTIONS: Participants received either 2000 IU/d of alpha tocopherol (n = 152), 20 mg/d of memantine (n = 155), the combination (n = 154), or placebo (n = 152). MAIN OUTCOMES AND MEASURES: Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory score (range, 0-78). Secondary outcomes included cognitive, neuropsychiatric, functional, and caregiver measures. RESULTS: Data from 561 participants were analyzed (alpha tocopherol = 140, memantine = 142, combination = 139, placebo = 140), with 52 excluded because of a lack of any follow-up data. Over the mean (SD) follow-up of 2.27 (1.22) years, ADCS-ADL Inventory scores declined by 3.15 units (95% CI, 0.92 to 5.39; adjusted P = .03) less in the alpha tocopherol group compared with the placebo group. In the memantine group, these scores declined 1.98 units less (95% CI, -0.24 to 4.20; adjusted P = .40) than the placebo group's decline. This change in the alpha tocopherol group translates into a delay in clinical progression of 19% per year compared with placebo or a delay of approximately 6.2 months over the follow-up period. Caregiver time increased least in the alpha tocopherol group. All-cause mortality and safety analyses showed a difference only on the serious adverse event of "infections or infestations," with greater frequencies in the memantine (31 events in 23 participants) and combination groups (44 events in 31 participants) compared with placebo (13 events in 11 participants). CONCLUSIONS AND RELEVANCE: Among patients with mild to moderate AD, 2000 IU/d of alpha tocopherol compared with placebo resulted in slower functional decline. There were no significant differences in the groups receiving memantine alone or memantine plus alpha tocopherol. These findings suggest benefit of alpha tocopherol in mild to moderate AD by slowing functional decline and decreasing caregiver burden. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00235716.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/fisiopatologia , Antioxidantes/uso terapêutico , Dopaminérgicos/uso terapêutico , Memantina/uso terapêutico , Vitamina E/uso terapêutico , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/enfermagem , Antioxidantes/efeitos adversos , Cuidadores , Inibidores da Colinesterase/uso terapêutico , Progressão da Doença , Dopaminérgicos/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Memantina/efeitos adversos , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Vitamina E/efeitos adversos
16.
Alzheimers Dement ; 10(1): 36-44, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23583234

RESUMO

BACKGROUND: Alzheimer's disease (AD) has been associated with both oxidative stress and excessive glutamate activity. A clinical trial was designed to compare the effectiveness of (i) alpha-tocopherol, a vitamin E antioxidant; (ii) memantine (Namenda), an N-methyl-D-aspartate antagonist; (iii) their combination; and (iv) placebo in delaying clinical progression in AD. METHODS: The Veterans Affairs Cooperative Studies Program initiated a multicenter, randomized, double-blind, placebo-controlled trial in August 2007, with enrollment through March 2012 and follow-up continuing through September 2012. Participants with mild-to-moderate AD who were taking an acetylcholinesterase inhibitor were assigned randomly to 2000 IU/day of alpha-tocopherol, 20 mg/day memantine, 2000 IU/day alpha-tocopherol plus 20 mg/day memantine, or placebo. The primary outcome for the study is the Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory. Secondary outcome measures include the Mini-Mental State Examination; the Alzheimer's Disease Assessment Scale, cognitive portion; the Dependence Scale; the Neuropsychiatric Inventory; and the Caregiver Activity Survey. Patient follow-up ranged from 6 months to 4 years. RESULTS: A total of 613 participants were randomized. The majority of the patients were male (97%) and white (86%), with a mean age of 79 years. The mean Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory score at entry was 57 and the mean Mini-Mental State Examination score at entry was 21. CONCLUSION: This large multicenter trial will address the unanswered question of the long-term safety and effectiveness of alpha-tocopherol, memantine, and their combination in patients with mild-to-moderate AD taking an acetylcholinesterase inhibitor. The results are expected in early 2013.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Antioxidantes/uso terapêutico , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Memantina/uso terapêutico , Vitamina E/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Estudos Longitudinais , Masculino , Escalas de Graduação Psiquiátrica , Veteranos
17.
Microb Biotechnol ; 17(1): e14383, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38231155

RESUMO

Microbial electrosynthesis (MES) constitutes a bioelectrochemical process where bacteria uptake electrons extracellularly from a polarized electrode to incorporate them into their anabolic metabolism. However, the efficiency of current MES reactor designs can be lower than expected due to limitations regarding electron transfer and mass transport. One of the most promising bioreactor configurations to overcome these bottlenecks is the Microbial Electrochemical Fluidized Bed Reactor (ME-FBR). In this study, microbial CO2 fixation is investigated for the first time in a ME-FBR operated as a 3-phase reactor (solid-liquid-gas). An electroconductive carbon bed, acting as a working electrode, was fluidized with gas and polarized at different potentials (-0.6, -0.8 and -1 V vs. Ag/AgCl) so it could act as an electron donor (biocathode). Under these potentials, CO2 fixation and electron transfer were evaluated. Autotrophic electroactive microorganisms from anaerobic wastewater were enriched in a ME-FBR in the presence of 2-bromoethanosulfonic acid (BES) to inhibit the growth of methanogens. Cyclic voltammetry analysis revealed interaction between the microorganisms and the cathode. Furthermore, volatile fatty acids like propionate, formate and acetate were detected in the culture supernatant. Acetate production had a maximum rate of ca. 1 g L-1 day-1 . Planktonic cell biomass was produced under continuous culture at values as high as ca. 0.7 g L-1 dry weight. Overall, this study demonstrates the feasibility of employing a fluidized electrode with gaseous substrates and electricity as the energy source for generating biomass and carboxylic acids.


Assuntos
Dióxido de Carbono , Ácidos Graxos Voláteis , Dióxido de Carbono/metabolismo , Biomassa , Acetatos , Eletrodos
19.
Microb Biotechnol ; 16(3): 569-578, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36537073

RESUMO

Purple phototrophic bacteria are one of the main actors in chemolithotrophic carbon fixation and, therefore, fundamental in the biogeochemical cycle. These microbes are capable of using insoluble electron donors such as ferrous minerals or even carbon-based electrodes. Carbon fixation through extracellular electron uptake places purple phototrophic bacteria in the field of microbial electrosynthesis as key carbon capturing microorganisms. In this work we demonstrate biomass production dominated by purple phototrophic bacteria with a cathode (-0.6 V vs. Ag/AgCl) as electron donor. In addition, we compared the growth and microbial population structure with ferrous iron as the electron donor. We detect interaction between the cathode and the consortium showing a midpoint potential of 0.05 V (vs. Ag/AgCl). Microbial community analyses revealed different microbial communities depending on the electron donor, indicating different metabolic interactions. Electrochemical measurements together with population analyses point to Rhodopseudomonas genus as the key genus in the extracellular electron uptake. Furthermore, the genera Azospira and Azospirillum could play a role in the photoelectrotrophic consortium.


Assuntos
Rodopseudomonas , Biomassa , Ferro/metabolismo , Eletricidade , Carbono/metabolismo , Eletrodos
20.
Front Microbiol ; 14: 1115956, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36992932

RESUMO

The climate crisis requires rethinking wastewater treatment to recover resources, such as nutrients and energy. In this scenario, purple phototrophic bacteria (PPB), the most versatile microorganisms on earth, are a promising alternative to transform the wastewater treatment plant concept into a biorefinery model by producing valuable protein-enriched biomass. PPB are capable of interacting with electrodes, exchanging electrons with electrically conductive materials. In this work, we have explored for mobile-bed (either stirred or fluidized) cathodes to maximize biomass production. For this purpose, stirred-electrode reactors were operated with low-reduced (3.5 e-/C) and high-reduced (5.9 e-/C) wastewater under cathodic polarization (-0.4 V and -0.8 V vs. Ag/AgCl). We observed that cathodic polarization and IR irradiation can play a key role in microbial and phenotypic selection, promoting (at -0.4 V) or minimizing (at -0.8 V) the presence of PPB. Then, we further study how cathodic polarization modulates PPB biomass production providing a fluid-like electrode as part of a so-called photo microbial electrochemical fluidized-bed reactor (photoME-FBR). Our results revealed the impact of reduction status of carbon source in wastewater to select the PPB photoheterotrophic community and how electrodes drive microbial population shifts depending on the reduction status of such carbon source.

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