RESUMO
Since the outbreak of COVID-19, mask wearing has become a global phenomenon. How do masks influence wearers' behavior in everyday life? We examine the effect of masks on wearers' deviant behavior in China, where mask wearing is mostly a public-health issue rather than a political issue. Drawing on behavioral ethics research, we test two competing hypotheses: (a) masks disinhibit wearers' deviant behavior by increasing their sense of anonymity and (b) masks are a moral symbol that reduces wearers' deviant behavior by heightening their moral awareness. The latter hypothesis was consistently supported by 10 studies (including direct replications) using mixed methods (e.g., traffic camera recording analysis, observational field studies, experiments, and natural field experiment) and different measures of deviant behavior (e.g., running a red light, bike parking in no-parking zones, cheating for money, and deviant behavior in the library). Our research (n = 68,243) is among the first to uncover the psychological and behavioral consequences of mask wearing beyond its health benefits.
Assuntos
COVID-19 , Máscaras , Princípios Morais , Simbolismo , COVID-19/prevenção & controle , China , Surtos de Doenças , Humanos , SARS-CoV-2RESUMO
Status dystonicus is the most severe form of dystonia with life-threatening complications if not treated promptly. We present consensus recommendations for the initial management of acutely worsening dystonia (including pre-status dystonicus and status dystonicus), as well as refractory status dystonicus in children. This guideline provides a stepwise approach to assessment, triage, interdisciplinary treatment, and monitoring of status dystonicus. The clinical pathways aim to: (1) facilitate timely recognition/triage of worsening dystonia, (2) standardize supportive and dystonia-directed therapies, (3) provide structure for interdisciplinary cooperation, (4) integrate advances in genomics and neuromodulation, (5) enable multicenter quality improvement and research, and (6) improve outcomes. © 2024 International Parkinson and Movement Disorder Society.
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Distúrbios Distônicos , Humanos , Criança , Distúrbios Distônicos/terapia , Distúrbios Distônicos/diagnóstico , Distonia/terapia , Distonia/diagnóstico , Gerenciamento ClínicoRESUMO
Culture and personality are two central topics in psychology. Individuals are culturally influenced influencers of culture, yet the research linking culture and personality has been limited and fragmentary. We integrate the literatures on culture and personality with recent advances in socioecology and genetics to formulate the Socioecological-Genetic Framework of Culture and Personality. Our framework not only delineates the mutual constitution of culture and personality but also sheds light on (a) the roots of culture and personality, (b) how socioecological changes partly explain temporal trends in culture and personality, and (c) how genes and culture/socioecology interact to influence personality (i.e., nature × nurture interactions). By spotlighting the roles of socioecology and genetics, our integrative framework advances the understanding of culture and personality.
Assuntos
Cultura , Personalidade , HumanosRESUMO
BACKGROUND: Mitochondrial genome sequences have become critical to the study of biodiversity. Genome skimming and other short-read based methods are the most common approaches, but they are not well-suited to scale up to multiplexing hundreds of samples. Here, we report on a new approach to sequence hundreds to thousands of complete mitochondrial genomes in parallel using long-amplicon sequencing. We amplified the mitochondrial genome of 677 specimens in two partially overlapping amplicons and implemented an asymmetric PCR-based indexing approach to multiplex 1,159 long amplicons together on a single PacBio SMRT Sequel II cell. We also tested this method on Oxford Nanopore Technologies (ONT) MinION R9.4 to assess if this method could be applied to other long-read technologies. We implemented several optimizations that make this method significantly more efficient than alternative mitochondrial genome sequencing methods. RESULTS: With the PacBio sequencing data we recovered at least one of the two fragments for 96% of samples (~ 80-90%) with mean coverage ~ 1,500x. The ONT data recovered less than 50% of input fragments likely due to low throughput and the design of the Barcoded Universal Primers which were optimized for PacBio sequencing. We compared a single mitochondrial gene alignment to half and full mitochondrial genomes and found, as expected, increased tree support with longer alignments, though whole mitochondrial genomes were not significantly better than half mitochondrial genomes. CONCLUSIONS: This method can effectively capture thousands of long amplicons in a single run and be used to build more robust phylogenies quickly and effectively. We provide several recommendations for future users depending on the evolutionary scale of their system. A natural extension of this method is to collect multi-locus datasets consisting of mitochondrial genomes and several long nuclear loci at once.
Assuntos
Genoma Mitocondrial , Sequenciamento por Nanoporos , Nanoporos , Análise de Sequência de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , BiodiversidadeRESUMO
The degree to which redox-driven proton pumps regulate net charge during electron transfer (ΔZET) remains undetermined due to difficulties in measuring the net charge of solvated proteins. Values of ΔZET can reflect reorganization energies or redox potentials associated with ET and can be used to distinguish ET from proton(s)-coupled electron transfer (PCET). Here, we synthesized protein "charge ladders" of a Rieske [2Fe-2S] subunit from Thermus thermophilus (truncTtRp) and made 120 electrostatic measurements of ΔZET across pH. Across pH 5-10, truncTtRp is suspected of transitioning from ET to PCET, and then to two proton-coupled ET (2PCET). Upon reduction, we found that truncTtRp became more negative at pH 6.0 by one unit (ΔZET = -1.01 ± 0.14), consistent with single ET; was isoelectric at pH 8.8 (ΔZET = -0.01 ± 0.45), consistent with PCET; and became more positive at pH 10.6 (ΔZET = +1.37 ± 0.60), consistent with 2PCET. These ΔZET values are attributed to protonation of H154 and H134. Across pH, redox potentials of TtRp (measured previously) correlated with protonation energies of H154 and H134 and ΔZET for truncTtRp, supporting a discrete proton pumping mechanism for Rieske proteins at the Fe-coordinating histidines.
Assuntos
Elétrons , Prótons , Transporte de Elétrons , Oxirredução , ProteínasRESUMO
PURPOSE: Health care insurance claims databases are becoming a more common data source for studies of medication safety during pregnancy. While pregnancies have historically been identified in such databases by pregnancy outcomes, International Classification of Diseases, 10th revision Clinical Modification (ICD-10-CM) Z3A codes denoting weeks of gestation provide more granular information on pregnancies and pregnancy periods (i.e., start and end dates). The purpose of this study was to develop a process that uses Z3A codes to identify pregnancies, pregnancy periods, and links infants within a commercial health insurance claims database. METHODS: We identified pregnancies, gestation periods, pregnancy outcomes, and linked infants within the US-based Optum Research Database between 2015 and 2020 via a series of algorithms utilizing diagnosis and procedure codes on claims. The diagnosis and procedure codes included ICD-10-CM codes, Current Procedural Terminology (CPT) codes, and Healthcare Common Procedure Coding System (HCPCS) codes. RESULTS: We identified 1 030 874 pregnancies among 841 196 women of reproductive age. Of pregnancies with livebirth outcomes, 84% were successfully linked to infants. The prevalence of pregnancy outcomes (livebirth, stillbirth, ectopic, molar, and abortion) was similar to national estimates. CONCLUSIONS: This process provides an opportunity to study drug safety and care patterns during pregnancy and may be replicated in other claims databases containing ICD-10-CM, CPT, and HCPCS codes. Work is underway to validate and refine the various algorithms.
Assuntos
Revisão da Utilização de Seguros , Classificação Internacional de Doenças , Demandas Administrativas em Assistência à Saúde , Current Procedural Terminology , Bases de Dados Factuais , Feminino , Humanos , GravidezRESUMO
BACKGROUND: The 2015 American Thyroid Association guidelines state that a prophylactic central compartment neck dissection (PCND) should be considered for patients with papillary thyroid carcinoma (PTC) and clinically involved lateral neck lymph nodes (cN1b). The purpose of our study was to determine the rate of central neck recurrence in select cN1b patients, with no evidence of clinically involved central compartment lymph nodes, treated without a PCND. METHODS: After institutional review board approval, adult PTC patients with cN1b disease who were treated with a total thyroidectomy and lateral neck dissection were identified from an institutional database of 6259 patients who underwent initial surgery for well-differentiated thyroid carcinoma from 1986 to 2015. Patients with gross extrathyroidal extension, distant metastases, or no preoperative imaging were excluded. Patients with evidence of clinically involved central compartment lymph nodes, on preoperative imaging or intraoperative evaluation, also were excluded. A total of 152 cN1b patients were included and categorized into non-PCND and PCND groups. Central neck recurrence-free probability (CNRFP) was calculated using the Kaplan-Meier method and log-rank tests. RESULTS: One hundred three patients (67.8%) did not have a PCND. With a median follow-up of 65 months, the 5- and 10-year CNRFP was 98.4% in the non-PCND group and 93.6% in the PCND group (p = 0.133). CONCLUSIONS: Select PTC patients with cN1b disease but no evidence of clinically involved central compartment lymph nodes, on preoperative imaging and intraoperative evaluation, appear to have a low rate of central neck recurrence. These patients may not require or benefit from a PCND.
Assuntos
Esvaziamento Cervical , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Tireoidectomia , Adulto , Humanos , Linfonodos/cirurgia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
BACKGROUND: Anti-programmed death protein 1 (anti-PD-1) agents have transformed the treatment of advanced melanoma and other cancers, but the rates of steroid-refractory toxicities and health care utilization are not well described. This study assessed these endpoints in patients with melanoma treated with anti-PD-1 with or without ipilimumab. METHODS: This study retrospectively evaluated 344 patients with metastatic melanoma treated with anti-PD-1 or a combination of ipilimumab and nivolumab at Vanderbilt University Medical Center from 2009 to 2018. The incidence, types, grades, management, and outcomes of immune-related adverse events (irAEs) and hospitalizations for irAEs and disease progression were assessed. RESULTS: Patients on combination therapy were more likely to develop irAEs than those on monotherapy (72% vs 37%; P < .001) and were more likely to require systemic steroids (61% vs 20%; P < .001), steroid dose re-escalation (23% vs 6%; P < .001), and second-line immunosuppressive use (17% vs 2%; P < .001) and to suffer high-dose steroid-refractory toxicities (23% vs 3%; P < .001). Combination-treated patients were more likely to have any hospitalization (32% vs 7%; P < .001) or multiple hospitalizations for irAEs (11% vs 3%; P = .001) and had a longer average time of hospitalization (mean, 1.92 vs 0.62 days; P = .002). Among 176 hospitalizations related to disease progression in patients who died during evaluable follow-up, 69% occurred within the 90 days before death. Early hospitalizations for disease-related reasons portended a very poor prognosis (median time from admission to death, 58 days). CONCLUSIONS: Patients treated with a combination of ipilimumab and nivolumab had higher rates of hospitalization and steroid-refractory toxicities than those treated with anti-PD-1 monotherapy. Disease-associated hospitalizations were similar between the 2 groups, portended a poor prognosis, and mostly occurred in the last months of life.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Melanoma/tratamento farmacológico , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Progressão da Doença , Resistência a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/imunologia , Feminino , Seguimentos , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Humanos , Ipilimumab/efeitos adversos , Masculino , Melanoma/imunologia , Melanoma/mortalidade , Melanoma/secundário , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Adulto JovemRESUMO
OBJECTIVES: Determine whether the insertion site of the recurrent laryngeal nerve (RLN) occurs at a predictable distance from the midline trachea, to help guide safe dissection during thyroid surgery. DESIGN: Prospective clinical trial. At the inferior edge of the cricoid cartilage, we measured the distance from mildline trachea to the RLN insertion site. SETTING: Single institution. PARTICIPANTS: 50 consecutive patients undergoing thyroid surgery. MAIN OUTCOME MEASURES: Distance from midline trachea to laryngeal insertion of RLN. RESULTS: The study population included 36 women and 14 men, with 72 total nerves measured. The average distance-to-midline + standard deviation (range) of the RLN was 20.7 + 2.3 (17-26) mm in women compared to 26.3 + 2.1 (22-32) mm in men. CONCLUSION: The insertion point of the RLN into the larynx at the level of inferior border of the cricoid cartilage can be reliably predicted, to facilitate early identification of the RLN during thyroid surgery.
Assuntos
Cartilagem Cricoide/anatomia & histologia , Laringe/anatomia & histologia , Nervo Laríngeo Recorrente/anatomia & histologia , Traqueia/anatomia & histologia , Dissecação , Feminino , Humanos , Masculino , Estudos Prospectivos , TireoidectomiaRESUMO
The CuA center is the initial electron acceptor in cytochrome c oxidase, and it consists of two copper ions bridged by two cysteines and ligated by two histidines, a methionine, and a carbonyl in the peptide backbone of a nearby glutamine. The two ligating histidines are of particular interest as they may influence the electronic and redox properties of the metal center. To test for the presence of reactive ligating histidines, a portion of cytochrome c oxidase from the bacteria Thermus thermophilus that contains the CuA site (the TtCuA protein) was treated with the chemical modifier diethyl pyrocarbonate (DEPC) and the reaction followed through UV-visible, circular dichroism, and electron paramagnetic resonance spectroscopies at pH 5.0-9.0. A mutant protein (H40A/H117A) with the non-ligating histidines removed was similarly tested. Introduction of an electron-withdrawing DEPC-modification onto the ligating histidine 157 of TtCuA increased the reduction potential by over 70 mV, as assessed by cyclic voltammetry. Results from both proteins indicate that DEPC reacts with one of the two ligating histidines, modification of a ligating histidine raises the reduction potential of the CuA site, and formation of the DEPC adduct is reversible at room temperature. The existence of the reactive ligating histidine suggests that this residue may play a role in modulating the electronic and redox properties of TtCuA through kinetically-controlled proton exchange with the solvent. Lack of reactivity by the metalloproteins Sco and azurin, both of which contain a mononuclear copper center, indicate that reactivity toward DEPC is not a characteristic of all ligating histidines.
Assuntos
Proteínas de Bactérias/química , Dietil Pirocarbonato/química , Complexo IV da Cadeia de Transporte de Elétrons/química , Histidina/química , Thermus thermophilus/química , Proteínas de Bactérias/metabolismo , Cobre/química , Cobre/metabolismo , Dietil Pirocarbonato/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Histidina/metabolismo , Modelos Moleculares , Oxirredução , Thermus thermophilus/enzimologia , Thermus thermophilus/metabolismoAssuntos
Amoxicilina , Antibacterianos , Hipersensibilidade a Drogas , Penicilinas , Humanos , Hipersensibilidade a Drogas/diagnóstico , Amoxicilina/efeitos adversos , Amoxicilina/administração & dosagem , Amoxicilina/imunologia , Criança , Penicilinas/efeitos adversos , Penicilinas/imunologia , Feminino , Antibacterianos/efeitos adversos , Antibacterianos/administração & dosagem , Masculino , Pré-Escolar , Testes Cutâneos/métodos , Adolescente , LactenteAssuntos
Hidradenite Supurativa , Sepse , Humanos , Hidradenite Supurativa/diagnóstico , Estudos Retrospectivos , Feminino , Masculino , Adulto , Sepse/epidemiologia , Pessoa de Meia-Idade , Exacerbação dos Sintomas , Adulto Jovem , Hospitalização/estatística & dados numéricos , Admissão do Paciente/estatística & dados numéricosRESUMO
In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.
Énoncé de position quant à l'utilisation du cannabis médical dans le traitement de l'épilepsie. L'utilisation du cannabis à des fins récréatives a été légalisée au Canada en octobre 2018. Parallèlement à ce changement de politique, de récentes publication visant à évaluer l'efficacité du cannabis dans le traitement de l'épilepsie, de même qu'une sensibilisation médiatique accrue en ce qui concerne son utilisation, ont eu pour effet d'augmenter l'intérêt du grand public à son égard. Le Comité médical thérapeutique de la Ligue canadienne contre l'épilepsie (LCCE), de concert avec un groupe multidisciplinaire d'experts et des représentants de l'Alliance canadienne de l'épilepsie, a ainsi élaboré un énoncé de position en ce qui regarde l'utilisation du cannabis médical dans le traitement de l'épilepsie. Cet article entend donc aborder le cadre légal qui prévaut actuellement au Canada et examiner de récentes publications s'étant penchées sur le profil sécuritaire et sur l'efficacité du cannabis. De plus, nous voulons apporter un éclairage au sujet des aspects cliniques dont il faudrait tenir compte au moment d'envisager l'utilisation du cannabis à des fins médicales.
Assuntos
Epilepsia/tratamento farmacológico , Maconha Medicinal/uso terapêutico , Canadá , HumanosRESUMO
BACKGROUND: Pediatric patients undergoing liver transplant are at significant risk for bleeding and thrombotic complications due to the complex nature of rebalanced hemostasis in patients with liver disease. METHODS/OBJECTIVES: We reviewed records of 92 pediatric liver and multivisceral transplant cases at Duke University Medical Center between January 2009 and December 2015. The goal was to define the nature and incidence of bleeding and thrombotic complications in this cohort and define potential risk factors. RESULTS: There were 24 major bleeding events in 19 transplants (incidence 20.7%) and 30 thrombotic events in 23 transplants (incidence 25%). Five of the 10 retransplantations were for vascular thrombotic complications. Thirty-day mortality was 4.9%, and three of these four deaths were due to vascular thrombosis. No bleeding events led to retransplantation or mortality. Prophylactic aspirin was associated with decreased risk of thrombosis without increased bleeding. Prophylactic heparin did not increase bleeding risk. Laboratory assays predicted events poorly, apparently failing to capture the nuanced and dynamic interplay between pro- and anticoagulant factors in the posttransplant patient. CONCLUSIONS: Both bleeding and thrombosis are frequent in this population, but only thrombotic complications contributed to retransplantation and mortality. A standardized approach to coagulation testing and antithrombotic therapy may be useful in predicting and reducing adverse outcomes. Alternative approaches to monitoring hemostasis need to be prospectively investigated in this complex patient population.
Assuntos
Hemorragia/etiologia , Hepatopatias/cirurgia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias , Trombose/etiologia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Fatores de RiscoRESUMO
OBJECTIVE: Limited evidence on the relationship between antiepileptic drug (AED) tapering and the likelihood of a seizure during an Epilepsy Monitoring Unit (EMU) admission is available, and no evidence specific to the pediatric population has been published. Our study sought to determine whether AED tapering leads to increased seizure likelihood in a pediatric EMU setting. METHODS: We performed a retrospective chart review of children admitted to the pediatric EMU at the Hospital for Sick Children in Toronto between June 1, 2014 and June 1, 2016. Data collected included demographics, reason for EMU referral, and epilepsy and medical characteristics. Among those with nondaily seizures, Kaplan-Meier curves were fit to compare probability of EMU seizure in those who were tapered fully from at least one AED to those not tapered. A Cox proportional hazards model was fit to evaluate this relationship after adjustment for subject sex, distance traveled to hospital, epilepsy duration, seizure frequency, time since last seizure, whether EMU referral was part of presurgical planning, magnetic resonance imaging (MRI) findings, and number of prescribed AEDs. An interaction between medication taper and number of prescribed AEDs was also included. Terms not significant at pâ¯<â¯0.3 were removed from the model, and the reduced model was recomputed. RESULTS: Of the 281 children included in the study, 159 had nondaily seizures. Kaplan-Meier curves indicated fully tapering at least one AED was associated with increased likelihood of seizure during EMU; however, after adjustment for confounding variables, this association was not preserved. Abnormal MRI findings, referral for presurgical evaluation, and shorter (≤3â¯months) time since last seizure were associated with increased likelihood of seizure during EMU. SIGNIFICANCE: Short-term AED tapering in pediatric patients may not be effective for increasing seizure likelihood in the EMU.
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Anticonvulsivantes/administração & dosagem , Monitoramento de Medicamentos/métodos , Epilepsia/diagnóstico por imagem , Epilepsia/tratamento farmacológico , Unidades Hospitalares , Adolescente , Criança , Pré-Escolar , Esquema de Medicação , Monitoramento de Medicamentos/tendências , Feminino , Unidades Hospitalares/tendências , Hospitalização/tendências , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Estudos Retrospectivos , Convulsões/diagnóstico por imagem , Convulsões/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: The aim of this study was to report our incidence of clinically evident neck recurrence, salvage neck management and subsequent outcomes in patients with papillary thyroid cancer. This is important to know so that patients with thyroid cancer can be properly counselled about the implications of recurrent disease and subsequent outcome. METHODS: An institutional database of 3664 patients with thyroid cancer operated between 1986 and 2010 was reviewed. Patients with nonpapillary histology and gross residual disease and those with distant metastases at presentation or distant metastases prior to nodal recurrence were excluded from the study. Of these, 99 (3.0%) patients developed clinically evident nodal recurrence. Details of recurrence and subsequent therapy were recorded for each patient. Subsequent disease-specific survival (sDSS), distant recurrence-free survival (sDRFS) and nodal recurrence-free survival (sNRFS) were determined from the date of first nodal recurrence using the Kaplan-Meier method. RESULTS: Of the 99 patients, 59% were female and 41% male. The median age was 41 years (range 5-91). The majority of patients had pT3/4 primary tumours (63%) and were pN+ (78%) at initial presentation. The median time to clinically evident nodal recurrence was 28 months (range: 3-264). Nodal recurrence occurred in the central neck in 15 (15%) patients, lateral neck in 74 (75%) patients and both in 10 (10%) patients. After salvage treatment, the 5-year sDSS was 97.4% from time of nodal recurrence. The 5-year sDRFS and sNRFS were 89.2% and 93.7%, respectively. CONCLUSION: In our series, isolated clinically evident nodal recurrence occurred in 3.0% of patients. Such patients are successfully salvaged with surgery and adjuvant therapy with sDSS of 97.4% at 5 years.
Assuntos
Carcinoma Papilar/patologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/mortalidade , Carcinoma Papilar/cirurgia , Carcinoma Papilar/terapia , Criança , Pré-Escolar , Terapia Combinada , Bases de Dados Factuais , Gerenciamento Clínico , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Recidiva Local de Neoplasia , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/terapia , Resultado do Tratamento , Adulto JovemRESUMO
Rieske proteins play an essential role in electron transfer in the bc 1 complex. Rieske proteins contain a [2Fe-2S] cluster with one iron ligated by two histidines and the other iron ligated by two cysteines. All Rieske proteins have pH-dependent reduction potentials with the histidines ligating the cluster deprotonating in response to increases in pH. The addition of diethylpyrocarbonate (DEPC) modifies deprotonated histidines. The previous studies on the isolated Thermus thermophilus Rieske protein have used large excesses of DEPC, and this study examines what amino acids become modified under different molar equivalents of DEPC to protein. Increasing amounts of DEPC result in more modification, and higher pH values result in faster reaction. Upon modification, the protein also becomes reduced and ~6 equivalents of DEPC are needed for 50% of the reduction to occur. Which amino acids are modified first also points to the most reactive species on the protein. Mass spectrometry analysis shows that lysine 68 is the most reactive amino acid, followed by the ligating histidine 154 and two other surfaces lysines, 76 and 43. The modification of the ligating histidine at low numbers of DEPC equivalents and correlation with a similar number of equivalents needed to reduce the protein shows that this histidine can interact with neighboring groups, and these results can be extended to the protein within the bc 1 complex, where interaction with neighboring residues or molecules may allow reduction to occur. These results may shed light on how Rieske transfers electrons and protons in the bc 1 complex.
Assuntos
Proteínas Ferro-Enxofre/química , Concentração de Íons de Hidrogênio , Proteínas Ferro-Enxofre/isolamento & purificação , Modelos Moleculares , Estrutura Molecular , OxirreduçãoRESUMO
BACKGROUND: Dairy products are a major contributor to dietary SFA. Partial replacement of milk SFA with unsaturated fatty acids (FAs) is possible through oleic-acid rich supplementation of the dairy cow diet. To assess adherence to the intervention of SFA-reduced, MUFA-enriched dairy product consumption in the RESET (REplacement of SaturatEd fat in dairy on Total cholesterol) study using 4-d weighed dietary records, in addition to plasma phospholipid FA (PL-FA) status. METHODS: In a randomised, controlled, crossover design, free-living UK participants identified as moderate risk for CVD (n = 54) were required to replace habitually consumed dairy foods (milk, cheese and butter), with study products with a FA profile typical of retail products (control) or SFA-reduced, MUFA-enriched profile (modified), for two 12-week periods, separated by an 8-week washout period. A flexible food-exchange model was used to implement each isoenergetic high-fat, high-dairy diet (38% of total energy intake (%TE) total fat): control (dietary target: 19%TE SFA; 11%TE MUFA) and modified (16%TE SFA; 14%TE MUFA). RESULTS: Following the modified diet, there was a smaller increase in SFA (17.2%TE vs. 19.1%TE; p < 0.001) and greater increase in MUFA intake (15.4%TE vs. 11.8%TE; p < 0.0001) when compared with the control. PL-FA analysis revealed lower total SFAs (p = 0.006), higher total cis-MUFAs and trans-MUFAs (both p < 0.0001) following the modified diet. CONCLUSION: The food-exchange model was successfully used to achieve RESET dietary targets by partial replacement of SFAs with MUFAs in dairy products, a finding reflected in the PL-FA profile and indicative of objective dietary compliance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02089035 , date 05-01-2014.
Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/prevenção & controle , Dieta , Ácidos Graxos/sangue , Cooperação do Paciente , Fosfolipídeos/sangue , Adulto , Idoso , Estudos Cross-Over , Laticínios/análise , Gorduras na Dieta/administração & dosagem , Método Duplo-Cego , Ácidos Graxos/administração & dosagem , Ácidos Graxos Monoinsaturados/administração & dosagem , Ácidos Graxos Monoinsaturados/sangue , Ácidos Graxos Insaturados/administração & dosagem , Ácidos Graxos Insaturados/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations. METHODS AND FINDINGS: Plasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study across eight European countries. Country-specific hazard ratios (HRs) were estimated using Prentice-weighted Cox regression and pooled by random-effects meta-analysis. We also systematically reviewed published prospective studies on circulating PUFAs and T2D risk and pooled the quantitative evidence for comparison with results from EPIC-InterAct. In EPIC-InterAct, among long-chain n-3 PUFAs, α-linolenic acid (ALA) was inversely associated with T2D (HR per standard deviation [SD] 0.93; 95% CI 0.88-0.98), but eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not significantly associated. Among n-6 PUFAs, linoleic acid (LA) (0.80; 95% CI 0.77-0.83) and eicosadienoic acid (EDA) (0.89; 95% CI 0.85-0.94) were inversely related, and arachidonic acid (AA) was not significantly associated, while significant positive associations were observed with γ-linolenic acid (GLA), dihomo-GLA, docosatetraenoic acid (DTA), and docosapentaenoic acid (n6-DPA), with HRs between 1.13 to 1.46 per SD. These findings from EPIC-InterAct were broadly similar to comparative findings from summary estimates from up to nine studies including between 71 to 2,499 T2D cases. Limitations included potential residual confounding and the inability to distinguish between dietary and metabolic influences on plasma phospholipid PUFAs. CONCLUSIONS: These large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA (ALA) but no convincing association of marine-derived n3 PUFAs (EPA and DHA) with T2D. Moreover, they highlight that the most abundant n6-PUFA (LA) is inversely associated with T2D. The detection of associations with previously less well-investigated PUFAs points to the importance of considering individual fatty acids rather than focusing on fatty acid class.