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The trapped-ion quantum charge-coupled device (QCCD) proposal1,2 lays out a blueprint for a universal quantum computer that uses mobile ions as qubits. Analogous to a charge-coupled device (CCD) camera, which stores and processes imaging information as movable electrical charges in coupled pixels, a QCCD computer stores quantum information in the internal state of electrically charged ions that are transported between different processing zones using dynamic electric fields. The promise of the QCCD architecture is to maintain the low error rates demonstrated in small trapped-ion experiments3-5 by limiting the quantum interactions to multiple small ion crystals, then physically splitting and rearranging the constituent ions of these crystals into new crystals, where further interactions occur. This approach leverages transport timescales that are fast relative to the coherence times of the qubits, the insensitivity of the qubit states of the ion to the electric fields used for transport, and the low crosstalk afforded by spatially separated crystals. However, engineering a machine capable of executing these operations across multiple interaction zones with low error introduces many difficulties, which have slowed progress in scaling this architecture to larger qubit numbers. Here we use a cryogenic surface trap to integrate all necessary elements of the QCCD architecture-a scalable trap design, parallel interaction zones and fast ion transport-into a programmable trapped-ion quantum computer that has a system performance consistent with the low error rates achieved in the individual ion crystals. We apply this approach to realize a teleported CNOT gate using mid-circuit measurement6, negligible crosstalk error and a quantum volume7 of 26 = 64. These results demonstrate that the QCCD architecture provides a viable path towards high-performance quantum computers.
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Background: Aortic stenosis (AS) is the world's most prevalent heart valve disease. Transcatheter aortic valve replacement (TAVR) or Implantation (TAVI) is widely available yet adopting this procedure in Asia has been slow due to high device cost, the need for specific training programs, and the lack of specialized heart teams and dedicated infrastructures. The limited number of randomized controlled trials describing TAVI outcomes among the Asian population hampered the approval for medical reimbursements as well as acceptance among surgeons and operators in some Asian countries. Methods: A comprehensive medical literature search on TAVI and/or TAVR performed in Asian countries published between January 2015 and June 2022 was done through MEDLINE and manual searches of bibliographies. The full text of eligible articles was obtained and evaluated for final analysis. The event rates for key efficacy and safety outcomes were calculated using the data from the registries and randomized controlled trials. Results: A total of 15,297 patients were included from 20 eligible studies. The mean patient age was 82.88 ± 9.94 years, with over half being females (62.01%). All but one study reported Society of Thoracic Surgeons (STS) scores averaging an intermediate risk score of 6.28 ± 1.06%. The mean logistic European Systems for Cardiac Operations Risk Evaluation (EuroSCORE) was 14.85. The mean baseline transaortic gradient and mean aortic valve area were 50.93 ± 3.70 mmHg and 0.64 ± 0.07 cm 2 , respectively. The mean procedural success rate was 95.28 ± 1.51%. The weighted mean 30-day and 1-year all-cause mortality rate was 1.66 ± 1.21% and 8.79 ± 2.3%, respectively. The mean average for stroke was 1.98 ± 1.49%. The acute kidney injury (AKI) rate was 6.88 ± 5.71%. The overall major vascular complication rate was 2.58 ± 2.54%; the overall major bleeding rate was 3.88 ± 3.74%. Paravalvular aortic regurgitation rate was 15.07 ± 9.58%. The overall rate of pacemaker insertion was 7.76 ± 4.6%. Conclusions: Compared to Americans and Europeans, Asian patients who underwent TAVI had lower all-cause mortality, bleeding, and vascular complications, however, had a higher rate of postprocedural aortic regurgitation. More studies with greater sample sizes are needed among Asian patients for a more robust comparison.
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BACKGROUND: Oral vardenafil (VDF) tablet is an effective treatment for erectile dysfunction (ED), but intranasal administration with a suitable formulation can lead to a faster onset of action and offer more convenient planning for ED treatment. AIM: The primary purpose of the present pilot clinical study was to determine whether intranasal VDF with an alcohol-based formulation can result in more "user-friendly pharmacokinetics" as compared with oral tablet administration. METHODS: This single-dose randomized crossover study was conducted in 12 healthy young volunteers receiving VDF as a 10-mg oral tablet or 3.38-mg intranasal spray. Multiple blood concentrations were obtained, and VDF concentrations were determined with a liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters following each treatment were compared and adverse events assessed. OUTCOMES: Pharmacokinetic parameters were obtained: apparent elimination rate constant, elimination half-life, peak concentration, peak time, total area under the curve, and relative bioavailability. RESULTS: Although mean apparent elimination rate constant, elimination half-life, peak concentration, and total area under the curve were similar between intranasal and oral administration, the median peak time from intranasal was much shorter (10 vs 58 minutes, P < .001, Mann-Whitney U test). The variability of the pharmacokinetic parameters was also less with intranasal than oral administration. The relative bioavailability of intranasal to oral was 1.67. Intranasal VDF caused transient but tolerable local nasal reactions in 50% of subjects. Other adverse events (eg, headache) were similar between the treatments. The incidence of adverse events was, however, significantly less in the second treatment after initial exposure to VDF. No serious adverse events were noted. CLINICAL IMPLICATIONS: Intranasal VDF potentially offers a more timely and lower dose for the treatment of ED in patients who can tolerate the transient local adverse reactions. STRENGTHS AND LIMITATIONS: The strength of this study is its randomized crossover design. Because the study was conducted in 12 healthy young subjects, the results may not reflect those observed in elderly patients who may be likely taking VDF for ED. Nevertheless, the changes of pharmacokinetic parameters in the present study are likely a reflection of the differences between intranasal and oral administration of the formulations. CONCLUSION: Our study indicated that the present VDF formulation, when administered intranasally, can achieve a more rapid but similar plasma concentration with only about one-third dose when compared with the oral administration.
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Disfunção Erétil , Masculino , Humanos , Idoso , Dicloridrato de Vardenafila , Administração Intranasal , Estudos Cross-Over , Disponibilidade Biológica , Área Sob a Curva , Comprimidos , Administração OralRESUMO
BACKGROUND: Since the inception of targeted therapies in treating lung cancer, providers have had to be aware of a new host of side effects when selecting management options for patients. Although targeted therapies are creating increased hope for patients with non-small cell lung cancers (NSCLC), understanding their side effects presents a challenge for providers. Alectinib, a second-generation tyrosine kinase inhibitor, is a targeted therapy used in patients with non-small cell lung cancer found to have anaplastic lymphoma kinase (ALK) mutations. Alectinib is the focus of this case report and literature review as we seek to understand side effects providers may encounter when prescribing these therapies. CASE PRESENTATION: We begin our report with the case of a 63-year-old Hispanic female with stage IIIA non-small cell lung cancer found to have the ALK genomic alteration. She was started on Alectinib, and on Day 11, she developed a severe maculopapular rash requiring hospitalization. After complete resolution, desensitization with Alectinib was attempted but unsuccessful. CONCLUSIONS: Despite the unsuccessful desensitization of this patient, it is important to report this rare side effect in order to better understand how providers can pursue management. Case reports such as this can aid providers in potentially preventing, treating, and rechallenging patients on targeted therapies in the future.
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Carcinoma Pulmonar de Células não Pequenas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Exantema , Neoplasias Pulmonares , Humanos , Feminino , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Exantema/induzido quimicamente , Exantema/tratamento farmacológicoRESUMO
BACKGROUND: Surgery remains the standard of care in rectal cancer. Select patients will not undergo surgery for reasons such as medical inoperability or a watch-and-wait approach and instead are managed with definitive chemoradiation. OBJECTIVE: We used the National Cancer Database to identify overall survival and predictors thereof in the nonoperative management of patients with rectal cancer. DESIGN: This was a retrospective review. SETTINGS: This study used deidentified data from the National Cancer Database. PATIENTS: We queried the national cancer database from 2004 to 2014 for stage 1 to 3 rectal adenocarcinoma treated with only chemotherapy and radiation to definitive doses. Dose escalated therapy was defined as >54 Gy. MAIN OUTCOME MEASURES: Univariable and multivariable analyses were performed to identify sociodemographic, treatment, and tumor characteristics predictive of dose escalation and overall survival. Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias. RESULTS: Among the 6311 patients eligible for the study, 11% were treated with doses >54 Gy. Earlier stage and increased age/comorbidity patients were more likely to receive dose escalation, and patients with more recent treatment and treatment at an academic facility were less likely. The median follow-up time was 31 months (range, 2-154 mo). Three- and 5-year overall survival rates for all patients were 60% and 46%. Patients treated with dose escalation had a median survival of 33 months compared with 56 months for those treated with ≤54 Gy (p < 0.0001). LIMITATIONS: The main limitation is the inherent selection bias present in National Cancer Database studies. Important treatment details and outcomes as they relate to a definitive chemoradiation approach in rectal cancer are lacking. Salvage therapy was also not recorded, which in this population could be surgery. CONCLUSIONS: In this analysis, dose escalation in the nonoperative management of rectal cancer was associated with a lower overall survival compared with more conventional doses. Careful patient selection and enrollment on appropriate clinical trials may be warranted in the nonoperative setting. See Video Abstract at http://links.lww.com/DCR/B15. LA QUIMIORRADIACIÓN DEFINITIVA PARA EL CÁNCER RECTAL: ¿HAY LUGAR PARA EL AUMENTO DE LA DOSIS? UN ESTUDIO DE BASE DE DATOS NACIONAL DEL CÁNCER:: La cirugía sigue siendo el estándar en el tratamiento del cáncer rectal. Algunos pacientes no son quirúrgicos por razones como, no ser operables o con el enfoque de ver y esperar, y en su lugar son tratados con la quimiorradiación definitiva.Utilizamos la base de datos nacional del cáncer para identificar la supervivencia general y los factores predictivos de la misma, en el tratamiento no quirúrgico de pacientes con cáncer rectal.Esta fue una revisión retrospectiva.Utilizamos los datos identificados en la base de datos nacional del cáncer.Se consultó la base de datos nacional del cáncer del 2004-2014, para adenocarcinoma rectal en estadio 1-3, tratada únicamente con quimioterapia y radiación hasta la dosis definitiva. La terapia de aumento de la dosis se definió como >54 Gy.Se realizaron análisis univariables y multivariables para identificar características sociodemográficas, de tratamiento y predictivas del aumento de la dosis y supervivencia en general. Los índices de riesgo proporcionales de Cox ajustados a la propensión para la supervivencia, se utilizaron para tener en cuenta el sesgo de indicación.Entre los 6311 pacientes elegibles para el estudio, el 11% fue tratado con dosis >54 Gy. Los pacientes en estadios tempranos y con mayor edad/comorbilidad, tenían más probabilidades de recibir aumento de la dosis, y menos propensos los pacientes con tratamientos recientes y de centros académicos. El tiempo medio de seguimiento fue de 31 meses (2-154 meses). Las tasas de supervivencia global de tres y cinco años para todos los pacientes, fueron respectivamente del 60% y 46%. Los pacientes tratados con aumento de la dosis, tuvieron una supervivencia media de 33 meses, en comparación con los 56 meses para los pacientes tratados con ≤54 Gy (p < 0,0001).La principal limitación es el inherente sesgo en la selección, presente en los estudios de la base de datos nacional del cáncer. Faltan los detalles importantes del tratamiento y los resultados en relación con el enfoque definitivo de quimiorradiación en cáncer rectal. Tampoco se registró la terapia de rescate, que en esta población podría ser la cirugía.En este análisis, el aumento de la dosis en el manejo no quirúrgico del cáncer rectal, se asoció con una menor supervivencia global, en comparación con la dosis más convencional. La cuidadosa selección del paciente y la inscripción en los apropiados ensayos clínicos, pueden estar justificados en el entorno no quirúrgico. Vea el Resumen del Video en http://links.lww.com/DCR/B15.
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Adenocarcinoma , Tratamento Conservador , Neoplasias Retais , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Quimiorradioterapia/métodos , Tratamento Conservador/métodos , Tratamento Conservador/estatística & dados numéricos , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Seleção de Pacientes , Pennsylvania/epidemiologia , Prognóstico , Pontuação de Propensão , Modelos de Riscos Proporcionais , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Estudos Retrospectivos , Análise de Sobrevida , Conduta Expectante/métodos , Conduta Expectante/estatística & dados numéricosRESUMO
Streptomycin was the first discovered aminoglycoside antibiotic. It has been widely applied in veterinary medicine for the prevention and treatment of bacterial infection. However, the current detection methods are not satisfactory in terms of sensitivity and sample process, which makes them unsuitable for a pharmacokinetic study. A high-performance liquid chromatography-mass spectrometric method employing positive electrospray ionization was developed and validated for the determination of streptomycin concentration in mice plasma. A simple protein precipitation method was utilized to extract streptomycin as well as the internal standard (kanamycin) from mouse plasma. This assay method was validated in terms of specificity, sensitivity, precision, accuracy and recovery. This method was applied to a pharmacokinetic study in mice following intramuscular administration of 200 mg/kg streptomycin. The lower limit of quantification of the developed assay method for streptomycin was 10 ng/mL. The intra-day and inter-day precision was evaluated with the coefficient of variations <14.3%, whereas the mean accuracy ranged from 87.0 to 105.0%. The samples were stable under the experimental conditions. The present method provides a robust, fast and sensitive analytical approach for the quantification of streptomycin in mouse plasma and has been successfully applied to a pharmacokinetic study in mice.
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Cromatografia Líquida de Alta Pressão/métodos , Estreptomicina/sangue , Estreptomicina/farmacocinética , Espectrometria de Massas em Tandem/métodos , Animais , Estabilidade de Medicamentos , Modelos Lineares , Camundongos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estreptomicina/químicaRESUMO
Background and objectives: Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular and metabolic risk factors, such as insulin resistance. Furthermore, OSAS has been associated with decreased levels of vitamin D (Vit D). The aim of the study was to assess the association between Vit D levels (expressed as 25(OH)D serum levels) and insulin resistance in patients with OSAS. Materials and Methods: Serum 25(OH)D levels were measured in consecutive subjects who had undergone polysomnography and pulmonary function testing. OSAS patients were divided into those with (homeostatic model assessment [HOMA-IR] ≥ 2) and without insulin resistance (HOMA-IR < 2). Results: Overall, 92 patients (81 males) were included in the study. OSAS patients with insulin resistance significantly differed from those without insulin resistance in terms of the body-mass index (BMI) (36.3 ± 5.8 compared to 32 ± 5.6 kg/m2, respectively, p = 0.001), apnoea-hypopnoea index (AHI) (57.4 ± 28.9 compared to 40.9 ± 27.9 events/h, respectively, p = 0.009) and indices of hypoxia during sleep. Patients with OSAS and insulin resistance had lower levels of serum 25 (OH) D compared with OSAS but without insulin resistance (19.3 ± 11.5 vs 26.7 ± 12.2 ng/mL, respectively, p = 0.005). Regression analysis demonstrated a negative association of 25(OH)D levels (ß = -0.048, odds ratio [OR]: 0.953, 95% confidence interval [CI]: 0.913-0.995, p = 0.030) and a positive association of BMI (ß = 0.110, OR: 1.116, 95% CI: 1.007-1.237, p = 0.036) with insulin resistance. Conclusions: Vit D insufficiency was significantly more frequent among OSAS patients with insulin resistance. Both low 25(OH)D levels and high BMI were associated with the risk of insulin resistance in this population.
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Resistência à Insulina/fisiologia , Apneia Obstrutiva do Sono/sangue , Deficiência de Vitamina D/complicações , Vitamina D/análise , Adulto , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia/métodos , Fatores de Risco , Sono/fisiologia , Apneia Obstrutiva do Sono/complicações , Estatísticas não Paramétricas , Vitamina D/sangue , Deficiência de Vitamina D/sangueRESUMO
PURPOSE OF REVIEW: Current data suggest that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may affect many metabolic pathways beyond lowering LDL cholesterol. The aim of the present manuscript is to present these so-called pleiotropic effects of PCSK9 inhibitors. RECENT FINDINGS: PCSK9 may affect the activity of other receptors beyond LDL receptors (LDLR), such as cluster of differentiation 36 (CD36), very-low-density-lipoprotein (VLDL) receptors, apolipoprotein (Apo) E receptors, LDLR-related protein 1 (LRP-1) and ATP-Binding Cassette Transporter (ABCA1). Thus, a role of PCSK9 in the development of atherosclerosis, in vascular wall inflammation and in platelet function has been suggested. Additionally, PCSK9 inhibitors may affect lipid variables beyond LDL cholesterol, carbohydrate variables, as well as they may affect brain and kidney function. Additionally, a controversial role of PCSK9 in sepsis, hepatitis C infection and Alzheimer's disease has been suggested. SUMMARY: These possible pleiotropic effects of PCSK9 inhibitors need further research, as they may affect cardiovascular risk and provide further insights in the development of atherosclerosis and other diseases such as Alzheimer's disease or chronic viral infection and sepsis.
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Inibidores de PCSK9 , Inibidores de Proteases/efeitos adversos , Humanos , Inibidores de Proteases/farmacologiaRESUMO
PURPOSE OF REVIEW: Chronic kidney disease (CKD) is recognized as a worldwide epidemic. Hypertension commonly coexists with CKD and its prevalence is progressively increasing as kidney function declines. RECENT FINDINGS: For patients with established CKD and/or diabetes with albuminuria, the updated hypertension guidelines have recommended a blood pressure (BP) goal < 130/80 mmHg. Blood pressure level above 130/80 mmHg in CKD patients requires lifestyle modifications and multiple antihypertensive medications. According to recent guidelines, angiotensin-converting enzyme (ACE) inhibitors should be the drugs of first choice. Angiotensin II receptor blockers (ARBs) should be used if the ACE inhibitor is not tolerated. Non-dihydropyridine CCBs consistently reduce albuminuria and slow the decline in kidney function. Dihydropyridine CCBs should not be used as monotherapy in proteinuric CKD patients but always in combination with a RAAS blocker. Diuretics are commonly used and represent the cornerstone in the management of CKD patients. All the other agents are used when treatment with the other primary agents have failed. In patients with CKD, an intensive BP goal < 130/80 mmHg has been recommended. We review current treatment options.
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Anti-Hipertensivos/farmacologia , Hipertensão , Insuficiência Renal Crônica , Albuminúria/diagnóstico , Albuminúria/etiologia , Anti-Hipertensivos/classificação , Progressão da Doença , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Testes de Função Renal , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologiaRESUMO
The three major ethnic groups of Nigerian population namely the Hausa, Igbo and Yoruba make up 29, 21 and 18% of the total population, respectively. To provide genetic information necessary for forensic analysis, this study was carried out to determine STR allele frequencies in 102 Hausa, 128 Igbo and 134 Yoruba individuals in Nigeria using 21 STR loci including the 20 CODIS (Combined DNA Index System) loci plus SE33.
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Etnicidade/genética , Genética Populacional , Repetições de Microssatélites , Impressões Digitais de DNA , Frequência do Gene , Variação Genética , Humanos , Nigéria/etnologiaRESUMO
In the original paper author Alani Sulaimon Akanmu was erroneously omitted from the author list. Prof. Akanmu has now been added as 4th author. Prof. Akanmu acted as an academic supervisor of the study and additionally contributed to the publication by reading, commenting and editing the manuscript.
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Recent studies suggest that the cholesterol content of HDL (high density lipoproteins) may provide limited information on their antiatherogenic properties and that the composition and particles' structure provide more information on their functionality. We used NMR-based (nuclear magnetic resonance-based) lipidomics to study the relationships of serum HDL-C (HDL-cholesterol) levels with the lipid composition of HDL particles in three groups of subjects selected on the basis of their HDL-C levels. Subjects with low and high HDL-C levels exhibited differences in HDL lipidome compared to those with normal HDL-C levels. In pattern recognition analysis, the discrimination power among all groups was of high significance. The low HDL-C group presented enrichment of the core in triglycerides and depletion in cholesterol esters, whereas the high HDL-C group showed a decrease in triglycerides content. Additionally, as HDL-C increases, all lipid classes are esterified with higher percentage of unsaturated than saturated fatty acids. In addition to the aforementioned differences, the surface layer is enriched in sphingomyelin and free cholesterol in the high HDL-C level group. NMR-based lipidomic analysis of HDL can be particularly useful since it provides insights into molecular features and helps in the characterization of the atheroprotective function of HDL lipoproteins and in the identification of novel biomarkers of cardiovascular risk.
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Doenças Cardiovasculares/sangue , HDL-Colesterol/sangue , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Lipoproteínas HDL/sangue , Adulto , Idoso , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Feminino , Voluntários Saudáveis , Humanos , Hipercolesterolemia/sangue , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fosfatidilcolinas/sangue , Fosfolipídeos/sangue , Esfingomielinas/sangueRESUMO
We demonstrate quantum entanglement of two trapped atomic ion qubits using a sequence of ultrafast laser pulses. Unlike previous demonstrations of entanglement mediated by the Coulomb interaction, this scheme does not require confinement to the Lamb-Dicke regime and can be less sensitive to ambient noise due to its speed. To elucidate the physics of an ultrafast phase gate, we generate a high entanglement rate using just ten pulses, each of â¼20 ps duration, and demonstrate an entangled Bell state with (76±1)% fidelity. These results pave the way for entanglement operations within a large collection of qubits by exciting only local modes of motion.
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Statins are first-line evidence-based drugs for the management of dyslipidaemias and to reduce the risk of cardiovascular events. However, statin clinical trials have shown marginally significant benefits on mortality, especially in the primary prevention setting. A major limitation of those trials is their relatively short follow-up. A reduced number of fatal events within a 5-year follow-up make mortality benefits unlikely to arise. This is particularly relevant for the primary prevention trials, where the risk of cardiovascular death is low. The short follow-up is a limitation for safety assessments too. However, extended major statin trials failed to detect any major safety concerns. Safety and efficacy assessments are even more complicated considering the differences of cardiovascular risk status in primary prevention individuals, and also given some potential ethnic and inter-individual genetic variations in response to statin treatment. Considerable evidence suggests a favourable risk-benefit balance for statin treatment. It can be assumed that statins reduce mortality in the long term by preventing cardiovascular events with complications that reduce lifespan. Unfortunately, this hypothesis cannot be proven as there is no current ethical basis on designing long-term placebo-controlled statin trials. Nevertheless, by effectively reducing disabilities related to cardiovascular events, statins have major benefits for public health. Therefore, clinicians should not withhold statin treatment awaiting proof of mortality benefits, as this may remain an 'untold story'.
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Doenças Cardiovasculares/prevenção & controle , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Dislipidemias/complicações , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Prevenção Primária , Fatores de RiscoRESUMO
PURPOSE OF REVIEW: Omega-3 fatty acids are increasingly used for the protection of cardiovascular disease. The main but not the sole mechanism of action is the reduction of triglyceride levels. In this review, we summarize the effect of omega-3 supplements on all-cause and cardiovascular mortality, myocardial infarction, and stroke from the relevant randomized controlled trials. RECENT FINDINGS: Twenty-one randomized controlled trials assessed omega-3 supplementation on mortality and cardiovascular-related outcomes. From these studies, as well as from the relevant meta-analyses, we found that omega-3 supplements do not exert a consistent benefit for cardiovascular protection. There is uncertainty of a clear profit from omega-3 supplementation in cardiovascular disease.
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Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Causas de Morte , Humanos , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/prevenção & controle , Triglicerídeos/sangueRESUMO
Among the epidemics of modern time, type 2 diabetes mellitus (T2DM) is one of the main contributors to overall morbidity as well as mortality. A number of different treatment options are available for the management of diabetes. Among them thiazolidinediones (TZDs) is an interesting drug class since it does not target the result of T2DM, i.e., hyperglycemia but rather some of the core mechanisms of the disease. Indeed, glitazones increase insulin sensitivity by activating the peroxisome proliferator-activated receptor γ, which plays an important role in regulating various metabolic parameters. Although TZDs have an established efficacy in T2DM treatment, their usage during the past years was questioned following the emergence of some alarming data regarding their safety and especially the cardiovascular safety of rosiglitazone. As a result, there is often some skepticism about the current role of TZDs in T2DM management. This mainly affects rosiglitazone even leading to its withdrawal from several markets in contrast to pioglitazone, which has shown a beneficial cardiovascular profile. A comprehensive assessment of the benefit-to-risk ratio of TZDs is required in order to better understand the place of these drugs in T2DM management.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Tiazolidinedionas/efeitos adversos , Tiazolidinedionas/uso terapêutico , Glicemia/metabolismo , Doenças Cardiovasculares/induzido quimicamente , Diabetes Mellitus Tipo 2/metabolismo , Fraturas Ósseas/induzido quimicamente , Humanos , Hipoglicemiantes/administração & dosagem , Resistência à Insulina , Fígado/efeitos dos fármacos , Fígado/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Tiazolidinedionas/administração & dosagem , Neoplasias da Bexiga Urinária/induzido quimicamenteRESUMO
Diagnosis of upper aerodigestive tract tumours using autofluorescence endoscopy in south east asian patients. OBJECTIVES: Autofluorescence is a highly sensitive, and specific, complementary diagnostic tool for the photodiagnosis of head and neck squamous cell carcinomas. Together with ease of use, these properties suggest that autofluorescence, used alongside white light endoscopy, could be a promising tool for the screening of high-risk populations. The aim of this study was to evaluate its effectiveness in detecting tumours involving the upper aerodigestive tract, in comparison with histopathologic examination. METHODOLOGY: A cross-sectional prospective study was carried out from June 2011 till March 2012. Forty-five patients with clinical evidence of suspicious lesions involving the upper aerodigestive tract were enrolled and examined using conventional white light, and autofluorescence endoscopy. A biopsy of each lesion was subsequently submitted for histopathologic examination. RESULTS: Using histology as our gold standard, we compared the sensitivity, specificity, and predictive values of autofluorescence endoscopy in detecting upper aerodigestive tract tumours. In comparison to histopathologic examination, the sensitivity of autofluorescence endoscopy was 95%, with a specificity of 74% (P value<0.001). The positive and negative predictive values were 78%, and 94% respectively. These data confirm a statistically significant correlation between autofluorescence and histopathologic diagnoses. CONCLUSIONS: Autofluorescence endoscopy was effective in detecting upper aerodigestive tract tumours, with excellent discrimination between benign and malignant phenotypes; this methodology is an ideal adjunct to white light endoscopy.
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Endoscopia/métodos , Neoplasias de Cabeça e Pescoço/patologia , Imagem Óptica , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Lymphangiomas are congenital malformations of the lymphatic system with characteristic dilated endothelium-lined spaces. It is vulnerability to infection or chemical irritants cause spontaneous reduction in size and in some cases complete resolution. Intralesional injection of OK-432 or Picibanil (lyophilized incubation mixture of Group A Streptococcus pyogenes of human origin) is slowly gaining recognition as its safety and efficacy standards have shown to avoid complications resulting from surgical interventions. The objective of this study was to evaluate the clinical outcomes of cystic hygroma patients who received OK-432 injections. METHODS: In between 2011 and 2013, six patients with cystic hygroma received intralesional injection of OK-432. All the patients were assessed clinically and radiologically either via ultrasound, computer tomography (CT) or magnetic resonant imaging (MRI) prior to and after receiving the injections. Patients' response towards treatment was classified as total shrinkage, marked shrinkage (greater than 50% reduction in size), slight shrinkage (less than 50% reduction in size) or non-responsive to treatment. RESULTS: Mean duration of follow-up was 12 months. Total shrinkage was achieved in one patient, marked shrinkage in three patients and one patient experienced mild shrinkage. Only one out of the six patients showed no response to treatment. None of the patients in this study experienced serious complications or adverse effects post intralesional injection of OK-432. CONCLUSIONS: Intralesional OK-432 injection is an effective and safe alternative in treating cystic hygroma.
Assuntos
Antineoplásicos/administração & dosagem , Linfangioma Cístico/tratamento farmacológico , Picibanil/administração & dosagem , Humanos , Injeções Intralesionais , Linfangioma , Tomografia Computadorizada por Raios XRESUMO
Abnormal lipid composition and metabolism of plasma lipoproteins play a crucial role in the pathogenesis of coronary heart disease (CHD). A (1)H NMR-based lipidomic approach was used to investigate the correlation of coronary artery stenosis with the atherogenic (non-HDL) and atheroprotective (HDL) lipid profiles in 99 patients with CHD of various stages of disease and compared with 60 patients with normal coronary arteries (NCA), all documented in coronary angiography. The pattern recognition models created from lipid profiles predicted the presence of CHD with a sensitivity of 87% and a specificity of 88% in the HDL model and with 90% and 89% in the non-HDL model, respectively. Patients with mild, moderate, and severe coronary artery stenosis were progressively differentiated from those with NCA in the non-HDL model with a statistically significant separation of severe stage from both mild and moderate. In the HDL model, the progressive differentiation of the disease stages was statistically significant only between patients with mild and severe coronary artery stenosis. The lipid constituents of lipoproteins that mainly characterized the initial stages and then the progression of the disease were the high levels of saturated fatty acids in lipids in both HDL and non-HDL particles, the low levels of HDL-phosphatidylcholine, HDL-sphingomyelin, and omega-3 fatty acids and linoleic acid in lipids in non-HDL particles. The conventional lipid marker, total cholesterol, found in low levels in HDL and in high levels in non-HDL, also contributed to the onset of the disease but with a much lower coefficient of significance. (1)H NMR-based lipidomic analysis of atherogenic and atheroprotective lipoproteins could contribute to the early evaluation of the onset of coronary artery disease and possibly to the establishment of an appropriate therapeutic option.
Assuntos
Doença das Coronárias/sangue , Metabolismo dos Lipídeos , Lipoproteínas/sangue , Lipoproteínas/metabolismo , Espectroscopia de Prótons por Ressonância Magnética/métodos , Idoso , Aterosclerose , Doença das Coronárias/patologia , Vasos Coronários/metabolismo , Progressão da Doença , Feminino , Humanos , Lipoproteínas HDL/sangue , Lipoproteínas HDL/metabolismo , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
We investigate theoretically the suppression of two-body losses when the on-site loss rate is larger than all other energy scales in a lattice. This work quantitatively explains the recently observed suppression of chemical reactions between two rotational states of fermionic KRb molecules confined in one-dimensional tubes with a weak lattice along the tubes [Yan et al., Nature (London) 501, 521 (2013)]. New loss rate measurements performed for different lattice parameters but under controlled initial conditions allow us to show that the loss suppression is a consequence of the combined effects of lattice confinement and the continuous quantum Zeno effect. A key finding, relevant for generic strongly reactive systems, is that while a single-band theory can qualitatively describe the data, a quantitative analysis must include multiband effects. Accounting for these effects reduces the inferred molecule filling fraction by a factor of 5. A rate equation can describe much of the data, but to properly reproduce the loss dynamics with a fixed fillingfraction for all lattice parameters we develop a mean-field model and benchmark it with numerically exacttime-dependent density matrix renormalization group calculations.