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2.
Phys Rev Lett ; 129(18): 187203, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36374676

RESUMO

We report the control of Rashba spin-orbit interaction by tuning asymmetric hybridization between Ti orbitals at the LaAlO_{3}/SrTiO_{3} interface. This asymmetric orbital hybridization is modulated by introducing a LaFeO_{3} layer between LaAlO_{3} and SrTiO_{3}, which alters the Ti-O lattice polarization and traps interfacial charge carriers, resulting in a large Rashba spin-orbit effect at the interface in the absence of an external bias. This observation is verified through high-resolution electron microscopy, magnetotransport and first-principles calculations. Our results open hitherto unexplored avenues of controlling Rashba interaction to design next-generation spin orbitronics.

3.
Nat Commun ; 13(1): 743, 2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35136053

RESUMO

Nickel-based complex oxides have served as a playground for decades in the quest for a copper-oxide analog of the high-temperature superconductivity. They may provide clues towards understanding the mechanism and an alternative route for high-temperature superconductors. The recent discovery of superconductivity in the infinite-layer nickelate thin films has fulfilled this pursuit. However, material synthesis remains challenging, direct demonstration of perfect diamagnetism is still missing, and understanding of the role of the interface and bulk to the superconducting properties is still lacking. Here, we show high-quality Nd0.8Sr0.2NiO2 thin films with different thicknesses and demonstrate the interface and strain effects on the electrical, magnetic and optical properties. Perfect diamagnetism is achieved, confirming the occurrence of superconductivity in the films. Unlike the thick films in which the normal-state Hall-coefficient changes signs as the temperature decreases, the Hall-coefficient of films thinner than 5.5 nm remains negative, suggesting a thickness-driven band structure modification. Moreover, X-ray absorption spectroscopy reveals the Ni-O hybridization nature in doped infinite-layer nickelates, and the hybridization is enhanced as the thickness decreases. Consistent with band structure calculations on the nickelate/SrTiO3 heterostructure, the interface and strain effect induce a dominating electron-like band in the ultrathin film, thus causing the sign-change of the Hall-coefficient.

4.
AIDS Res Ther ; 18(1): 80, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34724931

RESUMO

BACKGROUND: The efficacy and tolerability of an antiretroviral regimen are important considerations for selection of HIV-1 infection maintenance therapy. Abacavir/lamivudine plus rilpivirine (ABC/3TC + RPV) has been shown in international studies to be effective and well-tolerated in virologically suppressed individuals. This study evaluated the effectiveness and safety of switching to ABC/3TC + RPV as maintenance therapy in virologically suppressed HIV-1 infected individuals in Singapore. METHODS: In this retrospective, single-centre study, we included individuals who were prescribed ABC/3TC + RPV, had HIV-1 viral load (VL) < 50 copies/ml immediately pre-switch, and had no documented history of resistance mutations or virologic failure to any of the components. The follow-up period was 48 ± 12 weeks. The primary outcome was the proportion of individuals who maintained virologic suppression of HIV-1 VL < 50 copies/ml at the end of follow-up period based on on-treatment analysis. The secondary outcomes were the resistance profiles associated with virologic failure, changes in immunologic and metabolic parameters, and the safety profile of ABC/3TC + RPV. RESULTS: A total of 222 individuals were included in the study. The primary outcome was achieved in 197 individuals [88.8%, 95% confidence interval: 83.7-92.4%]. There were 21 individuals (9.5%) who discontinued treatment for non-virologic reasons. The remaining 4 individuals experienced virologic failure, of whom, 3 of these individuals had developed emergent antiretroviral resistance and had HIV-1 VL > 500 copies/ml at the end of the 48 ± 12 weeks follow-up period. The remaining individual experienced sustained low level viremia and subsequently achieved viral suppression without undergoing resistance testing. A total of 49 adverse events were observed in 31 out of 222 individuals (14.0%), which led to 13 individuals discontinuing therapy. Neuropsychiatric adverse events were most commonly observed (53.1%). A statistically significant increase in CD4 was observed (p < 0.01), with a median absolute change of 31 cells/uL (interquartile range: - 31.50 to 140.75). No significant changes in lipid profiles were detected. CONCLUSION: ABC/3TC + RPV is a safe and effective switch option for maintenance therapy in virologically suppressed HIV-1 individuals with in Singapore.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Lamivudina , Fármacos Anti-HIV/efeitos adversos , Didesoxinucleosídeos , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , Lamivudina/efeitos adversos , Estudos Retrospectivos , Rilpivirina/efeitos adversos , Singapura/epidemiologia
5.
J Hosp Infect ; 112: 104-107, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33864893

RESUMO

Personal protective equipment (PPE) is essential for healthcare worker (HCW) safety. Conservation of PPE for clinical use during the COVID-19 pandemic reduced its availability for training, necessitating an innovative approach to sourcing high physical resemblance PPE (HPR-PPE). We present a case study of crowd-sourcing of HPR-PPE to train HCWs. Survey results indicated that HPR-PPE enabled high-fidelity practise of PPE application and removal, aided procedure recall, improved user confidence and was sufficiently similar to medical-grade PPE. HPR-PPE provided a novel and cost-effective alternative. We also demonstrated that medical-grade PPE can be sourced from non-medical institutions and businesses during a pandemic.


Assuntos
COVID-19/prevenção & controle , Pessoal de Saúde/educação , Controle de Infecções/métodos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Equipamento de Proteção Individual/provisão & distribuição , Estudos de Casos e Controles , Crowdsourcing , Equipamentos Médicos Duráveis , Humanos , Controle de Infecções/instrumentação , Pesquisa Qualitativa , Dispositivos de Proteção Respiratória , Treinamento por Simulação
6.
QJM ; 114(10): 706-714, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-33533902

RESUMO

BACKGROUND/INTRODUCTION: There are little data on outcomes of COVID-19 patients with the presence of fever compared to the presence of symptoms. AIM: We examined the associations between symptomology, presence of fever and outcomes of a COVID-19 cohort. DESIGN AND METHODS: Between 23 January and 30 April 2020, 554 COVID-19 patients were admitted to a tertiary hospital in Singapore. They were allocated into four groups based on symptomology and fever-Group 1: asymptomatic and afebrile, Group 2: symptomatic but afebrile, Group 3: febrile but asymptomatic and Group 4: symptomatic and febrile. The primary outcomes were intensive care unit (ICU) admissions and mortality. The composite end-point included ICU admissions, mortality or any COVID-19 related end-organ involvement. RESULTS: There were differences in ferritin (P=0.003), C-reactive protein (CRP) levels (P<0.001) and lymphopenia (P=0.033) across all groups, with the most favourable biochemical profile in Group 1, and the least in Group 4. Symptomatic groups (Groups 2 and 4) had higher ICU admissions (1.9% and 6.0%, respectively, P=0.003) than asymptomatic groups (Groups 1 and 3). Composite end-point was highest in Group 4 (24.0%), followed by Group 3 (8.6%), Group 2 (4.8%) and Group 1 (2.4%) (P<0.001). The presence of fever (OR 4.096, 95% CI 1.737-9.656, P=0.001) was associated with the composite end-point after adjusting for age, pulse rate, comorbidities, lymphocyte, ferritin and CRP. Presence of symptoms was not associated with the composite end-point. DISCUSSION/CONCLUSION: In this COVID-19 cohort, presence of fever was a predictor of adverse outcomes. This has implications on the management of febrile but asymptomatic COVID-19 patients.


Assuntos
COVID-19 , Humanos , SARS-CoV-2
7.
Br J Oral Maxillofac Surg ; 58(10): 1229-1234, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32718749

RESUMO

Oral and Maxillofacial Surgery (OMFS) is one of 10 surgical specialties recognised by the General Medical Council (GMC). The GMC states that newly qualified doctors should be familiar with a wide range of specialties and should refer patients appropriately. However, inadequate awareness of and exposure to OMFS in UK medical schools have been widely reported. Two independent investigators conducted a scoping review of all published articles that have evaluated the preparation of students in OMFS in UK undergraduate medical curricula. Our inclusion criteria were UK studies, articles published since inception, OMFS education, and relevance for undergraduate medical students. Data were extracted in accordance with recommendations by the National Health Service (NHS) Centre for Reviews and Dissemination. These were then analysed by qualitative synthesis. Our initial search yielded a total of 351 articles. Following application of the exclusion criteria according to PRISMA guidelines, 11 articles were included in the final analysis. Four main themes were identified: exposure to OMFS in the medical school curriculum, knowledge of OMFS conditions, knowledge of OMFS career progression, and ability to refer OMFS conditions appropriately. A consistent finding was that most medical students felt that they had insufficient exposure to and awareness of the specialty. All the papers recommended the need for change in the existing undergraduate medical curriculum. This review shows an overwhelming need for further development of OMFS in undergraduate medical curricula in the UK. However, there is insufficient primary research to show how best to achieve this. We propose that future research should focus on improvements in the quality of the current teaching methods and the adoption of new innovations to inspire and educate future doctors.


Assuntos
Educação de Graduação em Medicina , Estudantes de Medicina , Cirurgia Bucal , Currículo , Humanos , Medicina Estatal , Reino Unido
8.
Rev Sci Instrum ; 91(3): 033903, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32260020

RESUMO

In this study, we describe an advanced multi-functional, variable-energy positron beam system capable of measuring the energies of multiple "positron-induced" electrons in coincidence with the Doppler-shifted gamma photon resulting from the annihilation of the correlated positron. The measurements were carried out using the unique characteristics of the digital time-of-flight spectrometer and the gamma spectrometer available with the advanced positron beam system. These measurements have resulted in (i) the first digital time-of-flight spectrum of positron annihilation-induced Auger electrons generated using coincident signals from a high-purity Ge detector and a micro-channel plate, (ii) a two-dimensional array of the energy of Doppler-broadened annihilation gamma and the time-of-flight of positron-annihilation induced Auger electrons/secondary electrons measured in coincidence with the annihilation gamma photon, and (iii) the time-of-flight spectra of multiple secondary electrons ejected from a bilayer graphene surface as a result of the impact and/or annihilation of positrons. The novelty of the gamma-electron coincidence spectroscopy has been demonstrated by extracting the Doppler-broadened spectrum of gamma photons emitted due to the annihilation of positrons exclusively with 1s electrons of carbon. The width of the extracted Doppler-broadened gamma spectrum has been found to be consistent with the expected broadening of the annihilation gamma spectrum due to the momentum of the 1s electrons in carbon.

9.
J Laryngol Otol ; 134(4): 284-292, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32178742

RESUMO

OBJECTIVE: Recent studies have indicated a lack of ENT training at the undergraduate and post-graduate levels. This study aimed to review the impact of recent educational innovations in improving ENT training for medical students and junior doctors in the UK. METHODS: Three independent investigators conducted a literature search of published articles on ENT education. Included studies were analysed using qualitative synthesis methods. RESULTS: An initial search yielded 2008 articles; 44 underwent full-text evaluation and 5 were included for final analysis. Most included studies demonstrated benefits for students when compared to existing teaching standards in terms of objective assessment (knowledge and skills gained) or subjective assessment (confidence and preference) following implemented educational innovations. CONCLUSION: This study identified educational innovations developed in the past 15 years to enhance the teaching of core ENT competencies. More research is needed to establish their impact on the state of ENT medical education in the UK.


Assuntos
Educação de Graduação em Medicina/métodos , Corpo Clínico Hospitalar/educação , Otolaringologia/educação , Estudantes de Medicina/psicologia , Competência Clínica/normas , Currículo , Educação Médica , Estudos de Avaliação como Assunto , Conhecimentos, Atitudes e Prática em Saúde , Ensaios Clínicos Controlados não Aleatórios como Assunto , Publicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Autoimagem , Estudantes de Medicina/estatística & dados numéricos , Reino Unido/epidemiologia
10.
Phys Rev Lett ; 123(2): 026805, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31386492

RESUMO

We report charge transfer and built-in electric fields across the epitaxial SrNb_{x}Ti_{1-x}O_{3-δ}/Si(001) interface. Electrical transport measurements indicate the formation of a hole gas in the Si and the presence of built-in fields. Hard x-ray photoelectron measurements reveal pronounced asymmetries in core-level spectra that arise from these built-in fields. Theoretical analysis of core-level spectra enables built-in fields and the resulting band bending to be spatially mapped across the heterojunction. The demonstration of tunable charge transfer, built-in fields, and the spatial mapping of the latter, lays the groundwork for the development of electrically coupled, functional heterojunctions.

11.
J Nutr Health Aging ; 23(6): 578-585, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31233081

RESUMO

OBJECTIVES: Caregivers of hospitalized older adults experience elevated levels of stress and are at risk of poor health outcomes. There is a lack of screening tools based on self-reported caregiver variables incorporating both protective and risk factors, for early identification of at-risk caregivers. This study reports the development of a caregiver-centric screening tool to identify risk of depression at admission and predicts 3-month risk of depression and quality of life amongst caregivers of older adults with an unplanned admission. DESIGN, SETTING AND PARTICIPANTS: This prospective cohort study was conducted in the medical wards of a tertiary-care hospital from July 2015 to May 2017. We recruited family caregivers of patients aged 65 years and above who fulfilled the following criteria: a) unplanned admission, b) not residing in nursing homes; and c) requiring assistance in activities of daily living. MEASUREMENTS: We examined 11 candidate caregiver variables (mastery, burden and nine demographic variables). Risk of depression (score ≥8 on Hospital Anxiety and Depression Scale (HADS-D) depression subscale) was the primary outcome, and was assessed during the index admission. Logistic regression models were used to identify risk factors and risk scores (weights). The total risk scores were then stratified into three risk levels. Predictive validity of the screening tool was assessed using 3-months post-discharge risk of depression and health-related quality of life (HRQoL). RESULTS: The study included 274 caregiver-patient dyads. The mean (SD) age of the caregivers was 59 (10) years with 33.6% caregivers screening positive for risk of depression. The final model comprised three caregiver variables: mastery, burden and education. The total risk scores ranged from 0 to 6 and showed good discrimination (AUC:0.82, 95% CI: 0.77 to 0.87). Caregivers were classified into low-risk (0-1 points), intermediate-risk (2-4 points), and high-risk (5-6 points) groups, with corresponding rates of risk of depression (HADS-D≥8) of 10.7%, 44.6% and 73.3%, during admission. Relative risk rates of the intermediate- and high- risk group using the low-risk group as reference were 4.16 and 6.84 respectively. At 3-months post-discharge, the rates of caregivers at risk of depression or having poor HRQoL also increased corresponding to the three risk levels as per baseline, supporting the predictive validity of the tool. CONCLUSIONS/IMPLICATIONS: The caregiver-centric tool is a novel, practical, self-administered, relatively brief caregiver-centric instrument that can be used for rapid screening and stratification of caregivers at risk of depression. Uniquely, the tool comprised of assessment of protective factor (mastery) in addition to risk factors to provide a holistic assessment of the caregiver. It can be incorporated as part of older adults' admission evaluation so that prompt intervention can be rendered to their at-risk caregivers.


Assuntos
Cuidadores/normas , Depressão/psicologia , Programas de Rastreamento/métodos , Qualidade de Vida/psicologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
12.
Bone Joint Res ; 8(3): 107-117, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30997036

RESUMO

OBJECTIVES: Long bone defects often require surgical intervention for functional restoration. The 'gold standard' treatment is autologous bone graft (ABG), usually from the patient's iliac crest. However, autograft is plagued by complications including limited supply, donor site morbidity, and the need for an additional surgery. Thus, alternative therapies are being actively investigated. Autologous bone marrow (BM) is considered as a candidate due to the presence of both endogenous reparative cells and growth factors. We aimed to compare the therapeutic potentials of autologous bone marrow aspirate (BMA) and ABG, which has not previously been done. METHODS: We compared the efficacy of coagulated autologous BMA and ABG for the repair of ulnar defects in New Zealand White rabbits. Segmental defects (14 mm) were filled with autologous clotted BM or morcellized autograft, and healing was assessed four and 12 weeks postoperatively. Harvested ulnas were subjected to radiological, micro-CT, histological, and mechanical analyses. RESULTS: Comparable results were obtained with autologous BMA clot and ABG, except for the quantification of new bone by micro-CT. Significantly more bone was found in the ABG-treated ulnar defects than in those treated with autologous BMA clot. This is possibly due to the remnants of necrotic autograft fragments that persisted within the healing defects at week 12 post-surgery. CONCLUSION: As similar treatment outcomes were achieved by the two strategies, the preferred treatment would be one that is associated with a lower risk of complications. Hence, these results demonstrate that coagulated BMA can be considered as an alternative autogenous therapy for long bone healing.Cite this article: Z. X. H. Lim, B. Rai, T. C. Tan, A. K. Ramruttun, J. H. Hui, V. Nurcombe, S. H. Teoh, S. M. Cool. Autologous bone marrow clot as an alternative to autograft for bone defect healing. Bone Joint Res 2019;8:107-117. DOI: 10.1302/2046-3758.83.BJR-2018-0096.R1.

13.
Osteoarthritis Cartilage ; 27(1): 49-58, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30243947

RESUMO

OBJECTIVES: Pain sensitization could be a risk factor for poor outcomes after knee replacement surgery (KR) for knee osteoarthritis (KOA). We aimed to evaluate the association between pre-operative central and peripheral pain sensitization measured using a digital pressure algometer and KR outcomes. METHODS: Consecutive patients with severe KOA listed for KR were recruited. Sociodemographic and symptoms data were collected prior to surgery. Pre-operative pressure pain thresholds (PPTs) were measured using a digital pressure algometer at the index knee and forearm. Patient satisfaction at 6 and 12 months after KR was assessed using a 4-point Likert scale, and dichotomized to satisfied and dissatisfied to KR. Western Ontario and McMaster Universities Index (WOMAC) Pain and function was assessed. The associations between pre-operative PPTs with KR outcomes at 6 and 12 months were evaluated. RESULTS: Of the 243 patients recruited, response rate at 6 and 12 months were 95.5% and 96.7%. The dissatisfaction rates were 8.2% and 5.1% at 6 and 12 months. There was no statistically significant association between pre-operative index knee or forearm PPTs and patient satisfaction. PPTs measured at the knee, but not the forearm, were weakly associated with change in the WOMAC pain score at 12 months, after adjustment for confounding factors. CONCLUSION: Pre-operative central sensitization, measured by handheld digital algometry, was not statistically significantly associated with satisfaction or change in pain after KR. Pre-operative peripheral sensitization was associated with change in pain symptoms after KR; however, this association was weak and unlikely to be a meaningful predictor of KR outcome in clinical practice.


Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho/cirurgia , Limiar da Dor/fisiologia , Dor/etiologia , Idoso , Sensibilização do Sistema Nervoso Central/fisiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Medição da Dor/métodos , Satisfação do Paciente , Período Pré-Operatório , Índice de Gravidade de Doença , Resultado do Tratamento
14.
Med Sci Sports Exerc ; 50(2): 344-352, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28945675

RESUMO

PURPOSE: This study aimed to examine the effect of taurine ingestion on maximal voluntary muscle torque and power in trained male athletes with different caffeine habits. METHODS: Fourteen male athletes 21.8 ± 2.5 yr old were separated into caffeine and noncaffeine consumers to control for the effect of caffeine withdrawal on muscle function. On separate occasions, participants performed four isokinetic or three maximal isometric knee extensions with and without taurine (40 mg·kg body mass) after a double-blind, counterbalanced design. Muscle contractile performances were compared between the first sets as well as between the sets where these variables scored best. RESULTS: In response to isokinetic contraction, taurine treatment in the noncaffeine consumers resulted in a significant fall in first (-16.1%; P = 0.013) and best peak torque (-5.0%; P = 0.016) as well as in first (-17.7%; P = 0.015) and best power output (-8.0%; P = 0.008). In the caffeine consumers deprived of caffeine, taurine intake improved best power (5.2%; P = 0.045). With respect to the isometric variables, there was a significant decrease in the first (-5.1%; P = 0.002) and best peak torque (-4.3%; P = 0.032) in the noncaffeine group, but no effect in the group of caffeine consumers deprived of caffeine. Taurine ingestion increased blood taurine levels but had no effect on plasma amino acid levels. CONCLUSIONS: Taurine ingestion is detrimental to maximal voluntary muscle power and both maximal isokinetic and isometric peak torque in noncaffeine consumers, whereas taurine ingestion in caffeine-deprived caffeine consumers improves maximal voluntary muscle power but has no effect on other aspects of contractile performance.


Assuntos
Contração Muscular/efeitos dos fármacos , Força Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Taurina/administração & dosagem , Adulto , Cafeína/administração & dosagem , Método Duplo-Cego , Humanos , Masculino , Músculo Esquelético/fisiologia , Taurina/farmacologia , Torque , Adulto Jovem
15.
Nat Commun ; 8: 15358, 2017 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-28580936

RESUMO

In conventional metals, modification of electron trajectories under magnetic field gives rise to a magnetoresistance that varies quadratically at low field, followed by a saturation at high field for closed orbits on the Fermi surface. Deviations from the conventional behaviour, for example, the observation of a linear magnetoresistance, or a non-saturating magnetoresistance, have been attributed to exotic electron scattering mechanisms. Recently, linear magnetoresistance has been observed in many Dirac materials, in which the electron-electron correlation is relatively weak. The strongly correlated helimagnet CrAs undergoes a quantum phase transition to a nonmagnetic superconductor under pressure. Here we observe, near the magnetic instability, a large and non-saturating quasilinear magnetoresistance from the upper critical field to 14 T at low temperatures. We show that the quasilinear magnetoresistance may arise from an intricate interplay between a nontrivial band crossing protected by nonsymmorphic crystal symmetry and strong magnetic fluctuations.

16.
Bone Marrow Transplant ; 52(3): 363-371, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27797364

RESUMO

The refined disease risk index (DRI) is a powerful prognostic model based solely on the disease type and stage for predicting survival outcomes of various hematological malignancies after allogeneic transplant. Here, we analyzed our series of 690 patients transplanted over the past 15 years, and showed that besides overall survival (OS), the refined DRI is also able to segregate event-free survival and relapse mortality in our cohort of largely Southeast Asian patients with a long and complete follow-up. Stratification by refined DRI remains statistically significant even when broken down by specific diseases each with a smaller number of patients, as well as for a small subset of patients younger than 18 years old, providing a robust model for prognostication. Multivariable analysis shows that refined DRI, age, year of transplant and donor type are independent risk factors for OS. We further demonstrated here that prognostication for a given patient with a specific disease can be made more discriminating by integrating independent risk factors such as age and donor type with the refined DRI. The future development of prognostic system incorporating the refined DRI with patient- and transplant-related risk factors will provide a more precise estimate of transplant outcome.


Assuntos
Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Doadores de Tecidos , Adulto , Fatores Etários , Aloenxertos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Taxa de Sobrevida
17.
Clin Genet ; 91(4): 557-563, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27247049

RESUMO

Individuals with two or more copies of the MECP2 gene, located at Xq28, share clinical features and a distinct facial phenotype known as MECP2 Duplication syndrome. We have examined perinatal characteristics, early childhood development and medical co-morbidities in this disorder. The International Rett Syndrome Phenotype Database (InterRett), which collects information from caregivers and clinicians on individuals with Rett syndrome and MECP2 associated disorders, was used as the data source. Data were available on 56 cases (49 males and 7 females) with MECP2 Duplication syndrome. Median age at ascertainment was 7.9 years (range: 1.2-37.6 years) and at diagnosis 3.0 years (range: 3 weeks-37 years). Less than a third (29%) learned to walk. Speech deterioration was reported in 34% and only 20% used word approximations or better at ascertainment. Over half (55%) had been hospitalised for respiratory infections in the first 2 years of life. Just under half (44%) had seizures, occurring daily in nearly half of this group. The majority (89%) had gastrointestinal problems and a third had a gastrostomy. Following the recent demonstration of phenotype reversal in a mouse model of MECP2 Duplication, a clear understanding of the natural history is crucial to the design and implementation of future therapeutic strategies.


Assuntos
Deficiência Intelectual/genética , Deficiência Intelectual Ligada ao Cromossomo X/genética , Deficiência Intelectual Ligada ao Cromossomo X/fisiopatologia , Proteína 2 de Ligação a Metil-CpG/genética , Adolescente , Adulto , Animais , Criança , Pré-Escolar , Bases de Dados Genéticas , Feminino , Trato Gastrointestinal/fisiopatologia , Trato Gastrointestinal/cirurgia , Humanos , Lactente , Deficiência Intelectual/fisiopatologia , Estimativa de Kaplan-Meier , Transtornos do Desenvolvimento da Linguagem/genética , Transtornos do Desenvolvimento da Linguagem/fisiopatologia , Masculino , Deficiência Intelectual Ligada ao Cromossomo X/epidemiologia , Deficiência Intelectual Ligada ao Cromossomo X/terapia , Camundongos , Fenótipo , Síndrome de Rett/epidemiologia , Síndrome de Rett/genética , Síndrome de Rett/fisiopatologia , Adulto Jovem
18.
Carcinogenesis ; 37(7): 701-711, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27207661

RESUMO

Neuroendocrine prostate cancer (NEPC) has a poor prognosis, with a median survival of less than 1 year after diagnosis. Following androgen deprivation therapy, prostate adenocarcinoma cells have been observed to develop an androgen receptor-negative, terminally differentiated and indolent neuroendocrine-like phenotype. However, several molecular events, including interleukin 6 (IL-6) stimulation, in the prostate microenvironment result in the appearance of aggressive, highly proliferative castrate-resistant NEPC. In this study, we examined the mechanistic effects of a natural prenylflavonoid, icaritin (ICT), on neuroendocrine differentiation in IL-6-induced LNCaP cells and NEPC development in the male transgenic adenocarcinoma of the mouse prostate (TRAMP) model. TRAMP mice received daily intraperitoneal injection of ICT or vehicle. ICT induced apoptosis in prostate tumor, suppressed NEPC development and, accordingly, improved overall survival in TRAMP mice. Expression of neuroendocrine markers (synaptophysin) and androgen receptor in TRAMP mice and neuroendocrine-like LNCaP cells were inhibited by ICT. Suppression of neuroendocrine and NEPC development by ICT was associated with dose-dependent inhibitory effects on abnormally elevated IL-6/STAT3 and Aurora kinase A in vitro and in vivo Since ICT demonstrated favorable pharmacokinetic and safety profiles with marked enrichment in prostate tissues, our study provides evidence for the development of prenylflavonoid as a multimodal therapeutic agent against NEPC.


Assuntos
Aurora Quinase A/biossíntese , Carcinoma Neuroendócrino/tratamento farmacológico , Flavonoides/administração & dosagem , Interleucina-6/biossíntese , Neoplasias da Próstata/tratamento farmacológico , Fator de Transcrição STAT3/biossíntese , Animais , Aurora Quinase A/genética , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/patologia , Diferenciação Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-6/genética , Masculino , Camundongos , Camundongos Transgênicos , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Receptores Androgênicos/biossíntese , Receptores Androgênicos/genética , Fator de Transcrição STAT3/genética , Transdução de Sinais , Sinaptofisina/biossíntese , Sinaptofisina/genética , Microambiente Tumoral/efeitos dos fármacos
19.
J Eur Acad Dermatol Venereol ; 30(7): 1159-64, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27027485

RESUMO

BACKGROUND: Psoriasis has a negative psychological impact on patients, and may have repercussions on treatment outcomes. Despite this, the degree to which psoriatic patients suffer from psychiatric disorders has not received much attention in Singapore. OBJECTIVE: This prospective cross-sectional study was conducted to determine the frequency of anxiety and depression in a cohort of Singaporean patients with psoriasis, and explore its relationship with regards to physical disease severity and subjective quality of life. METHODS: 100 patients aged 21-60 years old who visited the National Skin Centre, Singapore from 2008 to 2009 were enrolled into the study. Anxiety and depression were quantified using the Hospital Anxiety and Depression Scale (HADS). Disease severity was quantified with the Psoriasis Area Severity Index (PASI) and quality of life measured with the Short Form (36) Health Survey (SF-36). RESULTS: Using the HADS, the mean score for anxiety was 6.9 and that for depression was 4.7. An anxiety disorder was suggested in 17%, while a depressive disorder was suggested in 15% of the study population. All eight domains of the SF-36 were significantly correlated with both anxiety and depression scores. Patients with moderate or severe psoriasis (on PASI) had worse depression scores than those with mild psoriasis. No association was found between anxiety scores and PASI. Neither was any significant correlation seen between anxiety and depression scores vs. patients' age, monthly income and duration of psoriasis. CONCLUSION: This study demonstrates the strong psychiatric morbidity in patients with psoriasis, for which further psychiatric evaluation should be considered.


Assuntos
Ansiedade/etiologia , Depressão/etiologia , Psoríase/psicologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Singapura , Adulto Jovem
20.
Acta Biomater ; 28: 193-204, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26384700

RESUMO

Given the wide spread clinical use of ceramic-based bone void fillers, we sought to determine the efficacy of an FDA-approved ß-tricalcium phosphate bone graft substitute (JAX™) in combination with a carboxymethyl cellulose (CMC) handling agent that included a particular heparan glycosaminoglycan (GAG) variant, herein referred to as HS3. Having recently demonstrated efficacy of a combination collagen/HS3 device, we further aimed to determine the support that HS3 could offer a handling agent used to administer a more tissue-relevant bone void filler. This study evaluated the JAX™-HS3 combination device in 1.5 cm critical-sized defects in the ulna bones of 27 male New Zealand White rabbits. Treatment groups consisted of JAX™ applied with CMC alone, or JAX™ with CMC containing either 30 µg or 100 µg of the HS3 GAG. Data based on radiographic, µCT, mechanical, and histological analyses at 4 and 8 weeks post-surgery, clearly demonstrate enhanced new bone formation in the JAX™-HS3 combination treated defects compared to treatment with JAX™ alone. The efficacy of such a combination advocates for inclusion of HS3 in handling agents used in the preparation of various bone void fillers being used in orthopaedic surgery. STATEMENT OF SIGNIFICANCE: Synthetic bone grafts and demineralized bone matrices are gaining prominence as alternatives to autologous and allogeneic bone grafts and are frequently administered in granular form, necessitating their combination with a handling agent. Typical handling agents include glycerol, gelatin, cellulose, hyaluronic acid and lecithin, formulated as hydrogels, which can be further enhanced by the addition of heparan sulfate (HS) glycosaminoglycans that augment the osteostimulatory properties of the graft. Here we assessed the efficacy of ß-TCP granules combined with a hydrogel consisting of carboxymethyl cellulose and the HS variant (HS3) previously shown to enhance osteogenic healing. The data advocates for HS3 to be included during the formulation of hydrogel-based carriers that support the various bone void fillers being used in orthopaedic surgery.


Assuntos
Fosfatos de Cálcio/administração & dosagem , Glicosaminoglicanos/administração & dosagem , Heparitina Sulfato/administração & dosagem , Próteses e Implantes , Ulna/anormalidades , Animais , Masculino , Camundongos , Microtomografia por Raio-X
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