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1.
J Clin Psychol ; 79(4): 1099-1112, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36417619

RESUMO

The aim of this study was to analyze the psychometric properties of the Purpose in Life Test-Short Form (PIL-SF), a brief self-report measure of the presence of meaning in life (MiL). Participants were 349 nonclinical Spanish undergraduates (225 women, 64.5%, and 124 men, 35.5%), age ranged between 18 and 26 years (M = 20.85; SD = 2.16). The PIL-SF, the Seeking of Noetic Goals-8 Items (SONG-8), the Satisfaction with Life Scale (SWLS), and the Oxford Happiness Questionnaire (OHQ) were used. Descriptive analysis, estimation of the internal consistency, and Confirmatory Factor Analysis of the PIL-SF were conducted, and correlations between the PIL-SF and the SONG-8, the SWLS, and the OHQ were calculated. The PIL-SF showed good internal consistency and an excellent fit as a unidimensional scale confirming its factorial structure. Regarding construct validity, correlations between the PIL-SF and SWLS (r= 0.59) and OHQ (r = 0.56) were positive, significant (p < 0.001), while correlation between PIL-SF and SONG-8 was negative, significant (r = -0.23, p < 0.001). The Spanish adaptation of PIL-SF seems to be a valid measure of MiL with good internal consistency.


Assuntos
Psicometria , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Análise Fatorial , Psicometria/métodos , Reprodutibilidade dos Testes , Autorrelato , Inquéritos e Questionários , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Espanha
2.
J Oncol Pharm Pract ; 28(1): 228-231, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34082632

RESUMO

Everolimus is an immunosuppressant agent used in organ transplantation and, more recently, in cancer therapy. It has demonstrated beneficial effects in breast cancer, renal cancer, and neuroendocrine tumours. However, the treatment is not without side effects, some of which are still little known. We report the case of a 56 year-old man with a diagnosis of neuroendocrine tumour who developed a complex regional pain syndrome (CRPS) secondary to treatment with everolimus. CRPS has been linked to treatments with everolimus in renal and breast cancer patients as well as in renal transplant patients. To our knowledge, this is the first case of CRPS in a neuroendocrine tumour patient on everolimus treatment.


Assuntos
Síndromes da Dor Regional Complexa , Tumores Neuroendócrinos , Distrofia Simpática Reflexa , Síndromes da Dor Regional Complexa/induzido quimicamente , Síndromes da Dor Regional Complexa/tratamento farmacológico , Everolimo/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/tratamento farmacológico
3.
Aten Primaria ; 54(10): 102458, 2022 10.
Artigo em Espanhol | MEDLINE | ID: mdl-36137444

RESUMO

OBJECTIVE: To assess the health status of the homeless population. DESIGN: Cross-sectional descriptive study. SETTING: Raval Sud Primary Care Health Center (Barcelona). PARTICIPANTS: Homeless legal age people who have slept rough at some point in their lives. MAIN MEASUREMENTS: Sociodemographic data and time in a situation of homelessness. Chronic pathologies, transmissible infectious diseases, mental illnesses and substance use disorders. HAD questionnaire on anxiety and depression. CVRS EQ-5D-3L questionnaire. Descriptive statistics. RESULTS: The information of 146 patients with a mean age of 51.6 years (SD=12.8), 87% male and a mean of 12 years (SD=11.9) in a situation of homelessness was analyzed. The burden of disease was compared between the CAS profile (Drug addiction center - Baluard) and the socio-sanitary profile (Arrels Foundation). CAS users presented higher percentages of substance use disorders, mental illnesses and transmissible infectious diseases. People with a socio-health profile presented a higher percentage of chronic diseases (respiratory, cardiovascular and oncological) and more than half presented an alcohol use disorder and a higher percentage of disease associated with its consumption. CONCLUSIONS: The homeless population presents a high burden of disease, especially for mental illness, addictions and transmissible infectious diseases. We believe that studies are necessary to evaluate the disease excess compared to the general population with its derived costs and to design new strategies to address this burden of disease and its specificity.


Assuntos
Pessoas Mal Alojadas , Transtornos Mentais , Saúde da População , Transtornos Relacionados ao Uso de Substâncias , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
4.
Int J Behav Med ; 28(3): 268-276, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32909153

RESUMO

BACKGROUND: In the past decades, behavioral medicine has attained global recognition. Due to its global reach, a critical need has emerged to consider whether the original definition of behavioral medicine is still valid, comprehensive, and inclusive, and to reconsider the main tasks and goals of the International Society of Behavioral Medicine (ISBM), as the umbrella organization in the field. The purpose of the present study was to (i) update the definition and scope of behavioral medicine and its defining characteristics; and (ii) develop a proposal on ISBM's main tasks and goals. METHOD: Our study used the Delphi method. A core group prepared a discussion paper. An international Delphi panel rated questions and provided comments. The panel intended to reach an a priori defined level of consensus (i.e., 70%). RESULTS: The international panel reached consensus on an updated definition and scope of behavioral medicine as a field of research and practice that builds on collaboration among multiple disciplines. These disciplines are concerned with development and application of behavioral and biomedical evidence across the disease continuum in clinical and public health domains. Consensus was reached on a proposal for ISBM's main tasks and goals focused on supporting communication and collaboration across disciplines and participating organizations; stimulating research, education, and practice; and supporting individuals and organizations in the field. CONCLUSION: The consensus on definition and scope of behavioral medicine and ISBM's tasks and goals provides a foundational step toward achieving these goals.

5.
Int J Cancer ; 147(3): 619-632, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31637709

RESUMO

We estimated mortality figures for 2019 in seven Latin American countries, with focus on breast cancer. We retrieved cancer death certification and population data from the WHO and PAHO databases. We obtained mortality statistics for Argentina, Brazil, Chile, Colombia, Cuba, Mexico and Venezuela for 1970-2015. We predicted current death numbers and age-standardised (world population) mortality rates using joinpoint regression models. Total cancer mortality is predicted to decline in all countries and both sexes, except Argentinian women. Cuba had the highest all cancer rates for 2019, 136.9/100,000 men and 90.4 women, while Mexico showed the lowest ones, 63.8/100,000 men and 61.9 women. Stomach cancer showed favourable trends over the whole period, while colorectal cancer only recently. Lung cancer rates declined in men, while in women they decreased slightly over the most recent years, only. In Cuban women, lung cancer rates overtook breast cancer ones. Breast cancer showed overall favourable trends, but rates are rising in young women. Prostate and uterine cancer had favourable trends. Pancreas, ovary, bladder and leukaemias showed slightly decreasing trends. Between 1990 and 2019, mortality from all neoplasms is predicted to fall by about 18% in Argentina, 26% in Chile, 14% in Colombia, 17% in Mexico and 13% in Venezuela, corresponding to almost 0.5 million avoided cancer deaths. No decline was observed in Brazil and Cuba. Of concern, the persisting high rates of (cervix) uterus cancer, the high lung cancer rates in Cuba, the possible increases in breast cancer in young women, and the lack of overall declines in Brazil, Cuba and Venezuelan men.


Assuntos
Mortalidade/tendências , Neoplasias/mortalidade , Adulto , Fatores Etários , Idoso , Neoplasias da Mama/mortalidade , Neoplasias Colorretais/mortalidade , Feminino , Humanos , América Latina/epidemiologia , Leucemia/mortalidade , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasias/classificação , Caracteres Sexuais , Neoplasias Gástricas/mortalidade , Adulto Jovem
6.
BMC Public Health ; 20(1): 1738, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203431

RESUMO

BACKGROUND: Improved colorectal cancer (CRC) survival rates have been reported over the last years, with more than half of these patients surviving more than 5 years after the initial diagnosis. Better understanding these so-called long-term survivors could be very useful to further improve their prognosis as well as to detect other problems that may cause a significant deterioration in their health-related quality of life (HRQoL). Cure models provide novel statistical tools to better estimate the long-term survival rate for cancer and to identify characteristics that are differentially associated with a short or long-term prognosis. The aim of this study will be to investigate the long-term prognosis of CRC patients, characterise long-term CRC survivors and their HRQoL, and demonstrate the utility of statistical cure models to analyse survival and other associated factors in these patients. METHODS: This is a single-centre, ambispective, observational follow-up study in a cohort of n = 1945 patients with CRC diagnosed between 2006 and 2013. A HRQoL sub-study will be performed in the survivors of a subset of n = 485 CRC patients for which baseline HRQoL data from the time of their diagnosis is already available. Information obtained from interviews and the clinical records for each patient in the cohort is already available in a computerised database from previous studies. This data includes sociodemographic characteristics, family history of cancer, comorbidities, perceived symptoms, tumour characteristics at diagnosis, type of treatment, and diagnosis and treatment delay intervals. For the follow-up, information regarding local recurrences, development of metastases, new tumours, and mortality will be updated using hospital records. The HRQoL for long-term survivors will be assessed with the EORTC QLQ-C30 and QLQ-CR29 questionnaires. An analysis of global and specific survival (competitive risk models) will be performed. Relative survival will be estimated and mixture cure models will be applied. Finally, HRQoL will be analysed through multivariate regression models. DISCUSSION: We expect the results from this study to help us to more accurately determine the long-term survival of CRC, identify the needs and clinical situation of long-term CRC survivors, and could be used to propose new models of care for the follow-up of CRC patients.


Assuntos
Sobreviventes de Câncer , Neoplasias Colorretais , Neoplasias Colorretais/terapia , Seguimentos , Humanos , Recidiva Local de Neoplasia , Qualidade de Vida , Inquéritos e Questionários
7.
Folia Phoniatr Logop ; 72(1): 22-28, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31117095

RESUMO

BACKGROUND: Exercises involving tube phonation in water (TPW) have emerged as an alternative to conventional voice therapy techniques. The objective was to determine whether the results of these techniques were comparable to each other for the treatment of voice pathology, as well as to compare the costs implicated in the delivery of each treatment. METHODS: A retrospective, descriptive, and observational study was performed that included all patients evaluated in our voice unit in 2015 who received vocal rehabilitation treatments. They were divided into two groups depending on the treatment technique used. The patients' voice was evaluated subjectively using the GRBAS scale. We compared the clinical results and the specific costs of each technique. RESULTS: A total of 55 patients were studied, of which 28 followed TPW exercises, and 27 underwent supervised vocal rehabilitation (SVR). Most of the patients who received TPW therapy were diagnosed with functional dysphonia, whereas functional-organic dysphonia was the most common pathology in the SVR group. Significant differences were evident when the total GRBAS scores were compared before and after the treatments, yet not when the GRBAS scores were compared between the two rehabilitation techniques. The incremental cost-effectiveness analysis revealed that TPW was less expensive than SVR, with both techniques proving to be equally effective in improving the pathological problems. CONCLUSIONS: TPW is similarly effective as SVR techniques in treating voice pathologies, yet it is significantly cheaper in terms of healthcare costs.


Assuntos
Disfonia , Treinamento da Voz , Disfonia/terapia , Humanos , Fonação , Estudos Retrospectivos , Qualidade da Voz , Água
9.
Ann Surg Oncol ; 26(8): 2631-2639, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31011905

RESUMO

BACKGROUND: Tumor human leukocyte antigen class I (HLA-I) expression plays an important role in T cell-mediated tumor rejection. Loss of HLA-I is associated with cancer progression and resistance to immunotherapy, including antibodies blocking programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) signaling. Our objective was to analyze a correlation between HLA-I, tumor immune infiltration, and PD-L1/PD-1 axis in bladder cancer in association with the clinicopathologic features of patients. METHODS: We analyzed 85 cryopreserved bladder tumors by immunohistochemistry to investigate the expression of HLA-I, PD-L1, PD-1, CD3, CD8, and CXC chemokine receptor 4 (CXCR4). The results were correlated with tumor stage and other clinicopathologic variables of patients. RESULTS: We found a strong positive correlation between tumor HLA-I expression and infiltration with CD3+ and CD8 + T cells. PD-L1 expression was positive in 15.5% of tumors and heterogeneous in 40.5%, and was linked to a more advanced tumor stage. The majority of HLA-I-positive/heterogeneous tumors also expressed PD-L1 and PD-1, which were significantly correlated with each other and with lymphocyte infiltration. Interestingly, the analysis of the simultaneous expression of both markers revealed that 85.2% of tumors with a positive/heterogeneous HLA-I phenotype and negative for PD-L1 were mostly non-invasive, representing a 'tumor rejection' immune phenotype. CONCLUSIONS: High tumor HLA-I expression with absence of PD-L1 provides bladder cancer with an immune rejection mechanism. Evaluation of PD-L1 and HLA-I together should be considered in bladder cancer and may provide a new predictive biomarker of tumor invasiveness and of the response to 'immune checkpoint' therapy.


Assuntos
Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Musculares/imunologia , Recidiva Local de Neoplasia/imunologia , Neoplasias da Bexiga Urinária/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/imunologia , Biomarcadores Tumorais/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Feminino , Seguimentos , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Metástase Linfática , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/metabolismo , Neoplasias Musculares/patologia , Neoplasias Musculares/cirurgia , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Microambiente Tumoral , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
10.
J Hum Evol ; 135: 102663, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31521027

RESUMO

Pathological conditions have been previously documented in the Middle Pleistocene Sima de los Huesos hominins from northern Spain, and several of these have clear behavioral implications. Within this fossil assemblage, Cranium 4 shows bilateral external auditory exostoses which have been preliminarily interpreted as causing a significant hearing loss in this individual. If confirmed, this would be the oldest recorded case of deafness in human history and could have important implications for the antiquity of this condition, as well as social interactions. To further investigate this case, the current study presents 3D reconstructions of the entire outer and middle ear, based on computed tomography scans of both temporal bones in Cranium 4. We established the degree of stenosis in both external auditory canals, showing that in both cases the degree of stenosis is less than 52% of the original cross-sectional area of each canal. Based on clinical studies in living humans, the buildup of wax due to the degree of stenosis in Cranium 4 is unlikely to have caused frequent external ear infections. In addition, we estimated the pattern of sound power transmission up to 5 kHz in both ears relying on a comprehensive model developed in the bioengineering literature and which has been applied previously to the Sima de los Huesos hominins. The model was modified to account for the peculiar shape of the pathological external ear canals in Cranium 4. The results show that this pathology had little to no influence on the sound power transmission in this individual. Thus, we conclude that the exostoses present in both ears of Cranium 4 did not significantly affect their hearing.


Assuntos
Perda Auditiva/patologia , Homem de Neandertal , Animais , Hominidae , Masculino , Espanha
11.
J Minim Access Surg ; 15(3): 262-264, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30416148

RESUMO

Retrorectal cystic hamartomas, or tailgut cysts, are complex congenital cystic lesions which arise from embryologic tissues. Fewer than 200 cases have been reported worldwide, with women outnumbering men by 3:1. They are asymptomatic in 50% of the cases; the remainder present with back pain or mass effect as the most common symptoms. Malignant transformation rarely occurs. Guided biopsy is controversial, while surgery is the therapy of choice. We report the case of a 31-year-old woman complaining about perineal and vague lower abdominal pain, who was submitted to magnetic resonance imaging, which revealed a multilocular cystic, well-circumscribed retrorectal mass. Subsequently, laparoscopic excision was successfully accomplished. Operative time was 175 min. Intra- and post-operative course was uneventful. Hospital stay was 75 h. While any malignancy suspicion should lead to open surgery, given the risk of rupture, we support the benefits of laparoscopy may also be applied.

12.
Immunogenetics ; 70(10): 647-659, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30145665

RESUMO

HLA class I (HLA-I) molecules play a crucial role in the presentation of tumor antigenic peptides to CD8+ T cells. Tumor HLA-I loss provides a route of immune escape from T cell-mediated killing. We analyzed HLA-I expression in 98 cryopreserved breast cancer tissues using a broad panel of anti-HLA-I antibodies. Genomic HLA-I typing was performed using DNA obtained from autologous normal breast tissue. Analysis of the loss of heterozygosity (LOH) in the HLA-I region of chromosome 6 (LOH-6) and in the ß2-microglobulin (B2M) region of chromosome 15 (LOH-15) was done by microsatellite amplification of DNA isolated from microdissected tumor areas. B2M gene sequencing was done using this DNA form HLA-I-negative tumors. Immunohistological analysis revealed various types of HLA-I alterations in 79 tumors (81%), including total HLA-I loss in 53 cases (54%) and partial loss in 16 samples (14%). In 19 cases (19%), HLA-I expression was positive. Using microsatellite analysis, we detected LOH in 36 cases out of 92 evaluated (39%), including 15 samples with only LOH-6, 14 with LOH-15, and seven tumors with LOH-6 and LOH-15 at the same time. Remarkably, we detected LOH-6 in eight tumors with positive HLA-I immunolabeling. We did not find any B2M mutations in HLA-I-negative breast tumors. In conclusion, LOH at chromosomes 6 and 15 has a high incidence in breast cancer and occurs in tumors with different HLA-I immunophenotypes. This common molecular mechanism of HLA-I alterations may reduce the ability of cytotoxic T lymphocytes  to kill tumor cells and negatively influence the clinical success of cancer immunotherapy.


Assuntos
Antígenos de Neoplasias/genética , Neoplasias da Mama/genética , Antígenos de Histocompatibilidade Classe I/genética , Perda de Heterozigosidade/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/imunologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 6/genética , Feminino , Antígenos de Histocompatibilidade Classe I/imunologia , Teste de Histocompatibilidade , Humanos , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Microglobulina beta-2/genética
13.
J Biol Chem ; 291(19): 10104-18, 2016 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-26933033

RESUMO

Lipopolysaccharide dispersed in the blood by Gram-negative bacteria can be a potent inducer of septic shock. One research focus has been based on antibody sequestration of lipid A (the endotoxic principle of LPS); however, none have been successfully developed into a clinical treatment. Comparison of a panel of anti-lipid A antibodies reveals highly specific antibodies produced through distinct germ line precursors. The structures of antigen-binding fragments for two homologous mAbs specific for lipid A, S55-3 and S55-5, have been determined both in complex with lipid A disaccharide backbone and unliganded. These high resolution structures reveal a conserved positively charged pocket formed within the complementarity determining region H2 loops that binds the terminal phosphates of lipid A. Significantly, this motif occurs in unrelated antibodies where it mediates binding to negatively charged moieties through a range of epitopes, including phosphorylated peptides used in diagnostics and therapeutics. S55-3 and S55-5 have combining sites distinct from anti-lipid A antibodies previously described (as a result of their separate germ line origin), which are nevertheless complementary both in shape and charge to the antigen. S55-3 and S55-5 display similar avidity toward lipid A despite possessing a number of different amino acid residues in their combining sites. Binding of lipid A occurs independent of the acyl chains, although the GlcN-O6 attachment point for the core oligosaccharide is buried in the combining site, which explains their inability to recognize LPS. Despite their lack of therapeutic potential, the observed motif may have significant immunological implications as a tool for engineering recombinant antibodies.


Assuntos
Anticorpos Monoclonais/imunologia , Regiões Determinantes de Complementaridade/imunologia , Epitopos/imunologia , Fragmentos Fab das Imunoglobulinas/imunologia , Lipídeo A/imunologia , Lipopolissacarídeos/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/metabolismo , Sítios de Ligação de Anticorpos , Regiões Determinantes de Complementaridade/química , Regiões Determinantes de Complementaridade/metabolismo , Cristalografia por Raios X , Epitopos/química , Epitopos/metabolismo , Fragmentos Fab das Imunoglobulinas/química , Fragmentos Fab das Imunoglobulinas/metabolismo , Lipídeo A/química , Lipídeo A/metabolismo , Lipopolissacarídeos/química , Lipopolissacarídeos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Dados de Sequência Molecular , Estrutura Terciária de Proteína , Homologia de Sequência de Aminoácidos
14.
J Hepatol ; 67(2): 302-309, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28336466

RESUMO

BACKGROUND & AIMS: Trends in hepatocellular carcinoma (HCC) mortality rates have increased over recent decades in most countries. It is also the third cause of cancer death worldwide. The aim of this study is to update global trends in HCC mortality to 2014, and predict trends in rates in the EU, USA and Japan to 2020. METHODS: Death certification data for HCC over the 1990-2014 period from the World Health Organization database were analyzed. Sixteen European, five American countries, and six other countries worldwide were included, as well as the EU as a whole. RESULTS: In European men, mortality rates were stable during the last decade (3.5/100,000). HCC mortality increased in Northern and Central Europe, and decreased in Southern Europe. In the USA, HCC mortality increased by 35% between 2002 and 2012, reaching 3.1/100,000 men in 2012; it is predicted to remain stable to 2020. Reduced mortality rates were observed in East Asia, although they remained around 10-24/100,000 men. In Japan, HCC mortality is predicted to decrease (5.4/100,000 men in 2020). Trends were favorable in the young, but unfavorable in middle aged, except in East Asia. Mortality rates were 3- to 5-fold lower in women than men in most regions, but trends were similar. CONCLUSIONS: Control of hepatitis B (HBV) and hepatitis C virus (HCV) infections has contributed to the decrease in HCC-related mortality in East Asia and Southern Europe. Unfavorable trends in other regions can be attributed to HCV (and HBV) epidemics in the 1960s and 1980s, alcohol consumption, increased overweight/obesity, and diabetes. Better management of cirrhosis, HCC diagnosis and treatment are also influencing the mortality trends worldwide. LAY SUMMARY: Mortality rates due to HCC have increased in many countries over recent decades. In this study, we updated worldwide mortality trends for HCC from 1990 to 2014, and predicted trends for some countries to 2020. We observed unfavorable trends in Northern and Central Europe, North and Latin America. East Asia showed an improvement, however mortality rates in this region were 2- to 5-fold higher than in most European countries and the Americas. Steady declines to 2020 are predicted for East Asia but not for Europe and the Americas.


Assuntos
Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Adulto , Carcinoma Hepatocelular/etiologia , Feminino , Saúde Global/tendências , Hepatite B Crônica/complicações , Hepatite B Crônica/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Humanos , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
15.
J Biol Chem ; 290(32): 19629-40, 2015 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-26085093

RESUMO

Septic shock is a leading cause of death, and it results from an inflammatory cascade triggered by the presence of microbial products in the blood. Certain LPS from Gram-negative bacteria are very potent inducers and are responsible for a high percentage of septic shock cases. Despite decades of research, mAbs specific for lipid A (the endotoxic principle of LPS) have not been successfully developed into a clinical treatment for sepsis. To understand the molecular basis for the observed inability to translate in vitro specificity for lipid A into clinical potential, the structures of antigen-binding fragments of mAbs S1-15 and A6 have been determined both in complex with lipid A carbohydrate backbone and in the unliganded form. The two antibodies have separate germ line origins that generate two markedly different combining-site pockets that are complementary both in shape and charge to the antigen. mAb A6 binds lipid A through both variable light and heavy chain residues, whereas S1-15 utilizes exclusively the variable heavy chain. Both antibodies bind lipid A such that the GlcN-O6 attachment point for the core oligosaccharide is buried in the combining site, which explains the lack of LPS recognition. Longstanding reports of polyspecificity of anti-lipid A antibodies toward single-stranded DNA combined with observed homology of S1-15 and A6 and the reports of several single-stranded DNA-specific mAbs prompted the determination of the structure of S1-15 in complex with single-stranded DNA fragments, which may provide clues about the genesis of autoimmune diseases such as systemic lupus erythematosus, thyroiditis, and rheumatic autoimmune diseases.


Assuntos
Anticorpos Monoclonais/química , Glicoconjugados/química , Fragmentos Fab das Imunoglobulinas/química , Lipídeo A/química , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/imunologia , Especificidade de Anticorpos , Ascite/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Doenças Autoimunes/patologia , Sítios de Ligação de Anticorpos , DNA de Cadeia Simples/química , DNA de Cadeia Simples/imunologia , Glicoconjugados/biossíntese , Glicoconjugados/imunologia , Fragmentos Fab das Imunoglobulinas/biossíntese , Fragmentos Fab das Imunoglobulinas/imunologia , Lipídeo A/imunologia , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Ligação Proteica , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Eletricidade Estática
16.
Chem Rec ; 16(2): 810-24, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26924257

RESUMO

This personal account describes our contribution to the design of selective fluorogenic probes for contaminants of high environmental impact. For this purpose, we have developed a new family of highly versatile fluorogenic reagents that were able to show large differences in their fluorescence in the presence of selected analytes. They were used in the preparation of fluorogenic probes for the detection of contaminants of high environmental impact which currently have no good solutions: phosphorylating agents, such as chemical weapons; methyl mercury(II); the cyanide anion; amino-acid metabolites, such as doping substances; and biogenic amine mimics, such as drugs of abuse and recreational drugs. The development of new materials for specific sensing was achieved by anchoring selected probes to silica nanomaterials, suitable for the selective detection of organic analytes in water for immediate application to toxicological or environmental purposes.


Assuntos
Poluentes Ambientais/análise , Corantes Fluorescentes/química , Indenos/química , Aminoácidos/análise , Aminas Biogênicas/análise , Substâncias para a Guerra Química/análise , Fluorescência , Células HEK293 , Humanos , Drogas Ilícitas/análise , Compostos de Metilmercúrio/análise
17.
Am J Hematol ; 91(7): 700-4, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27074204

RESUMO

Multiple myeloma is a heterogeneous disease with variable survival; this variability cannot be fully explained by the current systems of risk stratification. Early mortality remains a serious obstacle to further improve the trend toward increased survival demonstrated in recent years. However, the definition of early mortality is not standardized yet. Importantly, no study has focused on the impact of comorbidity on early mortality in multiple myeloma to date. Therefore, we analyzed the role of baseline comorbidity in a large population-based cohort of 621 real-life myeloma patients over a 31-year period. To evaluate early mortality, a sequential multivariate regression model at 2, 6, and 12 months from diagnosis was performed. It was demonstrated that comorbidity had an independent impact on early mortality, which is differential and time-dependent. Besides renal failure, respiratory disease at 2 months, liver disease at 6 months, and hepatitis virus C infection at 12 months, were, respectively, associated with early mortality, adjusting for other well-established prognostic factors. On the other hand, the long-term monitoring in our study points out a modest downward trend in early mortality over time. This is the first single institution population-based study aiming to assess the impact of comorbidity on early mortality in multiple myeloma. It is suggested that early mortality should be analyzed at three key time points (2, 6, and 12 months), in order to allow comparisons between studies. Comorbidity plays a critical role in the outcome of myeloma patients in terms of early mortality. Am. J. Hematol. 91:700-704, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Mieloma Múltiplo/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Comorbidade , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Sistema de Registros , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Adulto Jovem
18.
Rev Esp Enferm Dig ; 108(5): 287-91, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26181288

RESUMO

The main cause of morbimor-mortality after major liver surgery is the development of liver failure posthepatectomy(LFPH). Treatment must involve multiple options and will be aggressive from the beginning. We report a case of a patient with cholangiocarcinoma perihilar treated with surgery: right hepatectomy extended to sI + IVb with develop of LFPH and biliary fistula and being management successfully in a multidisciplinary way.


Assuntos
Fístula Biliar/cirurgia , Hepatectomia/efeitos adversos , Falência Hepática/etiologia , Falência Hepática/terapia , Complicações Pós-Operatórias/terapia , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia , Regeneração Hepática , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Tomografia Computadorizada por Raios X
19.
Anticancer Drugs ; 26(2): 224-6, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25304989

RESUMO

Patients with BRCA-1 and BRCA-2 germ line mutations are at an increased risk of developing pancreatic adenocarcinoma (PAC). In particular, the BRCA-2 mutation has been associated with a relative risk of developing PAC of 3.51. The BRCA-2 protein is involved in repair of double-stranded DNA breaks. Recent reports have suggested that in the setting of impaired DNA repair, chemotherapeutic agents that induce DNA damage, such as platinum-based antineoplastic drugs (platins) and poly(ADP-ribose) polymerase inhibitors (PARP inhibitors), have improved efficacy. However, because of the relative rarity of BRCA-related PAC, studies evaluating such agents in this setting are scarce. Patients with a known BRCA-2 mutation and PAC were retrospectively reviewed. Ten patients with PAC and BRCA-2 mutation were identified. Four patients (40%) were of Ashkenazi Jewish descent. Seven patients (70%) received platinum agents, two (20%) received mitomycin-C, one (10%) received a PARP inhibitor, and seven (70%) received a topoisomerase-I inhibitor. Overall, chemotherapy was well tolerated with expected side effects. Patients with a BRCA-2 mutation and PAC represent a group with a unique biology underlying their cancer. Chemotherapies such as platinum derivatives, mitomycin-C, topoisomerase-I inhibitors, and PARP inhibitors targeting DNA require further investigation in this population. Genetic testing may guide therapy in the future.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Antineoplásicos/uso terapêutico , Proteína BRCA2/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Judeus/genética , Masculino , Pessoa de Meia-Idade , Mitomicina/uso terapêutico , Compostos Organoplatínicos/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases , Estudos Retrospectivos , Inibidores da Topoisomerase I/uso terapêutico , Resultado do Tratamento
20.
J Org Chem ; 80(1): 30-9, 2015 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-25414966

RESUMO

The reaction of N-(2-phthalimidoethyl)-N-alkylisopropylamines and S2Cl2 gave 4-N-(2-phthalimidoethyl)-N-alkylamino-5-chloro-1,2-dithiol-3-thiones that quantitatively cycloadded to dimethyl or diethyl acetylenedicarboxylate to give stable thioacid chlorides, which in turn reacted with one equivalent of aniline or a thiole to give thioanilides or a dithioester. Several compounds of this series showed atropisomers that were studied by a combination of dynamic NMR, simulation of the signals, conformational analysis by DFT methods, and single crystal X-ray diffraction, showing a good correlation between the theoretical calculations, the experimental values of energies, and the preferred conformations in the solid state. The steric hindering of the crowded substitution at the central amine group was found to be the reason for the presence of permanent atropisomers in this series of compounds and the cause of a unique disposition of the thioxo group at close-to-right angles with respect to the plane defined by the 1,3-dithiole ring in the dithiafulvene derivatives, thus breaking the sulfur-sulfur hypervalent bond that is always found in this kind of compounds.


Assuntos
Enxofre/química , Tioamidas/química , Estrutura Molecular , Teoria Quântica , Rotação , Tioamidas/síntese química
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