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1.
Nature ; 551(7678): 75-79, 2017 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-29094693

RESUMO

Gravitational waves were discovered with the detection of binary black-hole mergers and they should also be detectable from lower-mass neutron-star mergers. These are predicted to eject material rich in heavy radioactive isotopes that can power an electromagnetic signal. This signal is luminous at optical and infrared wavelengths and is called a kilonova. The gravitational-wave source GW170817 arose from a binary neutron-star merger in the nearby Universe with a relatively well confined sky position and distance estimate. Here we report observations and physical modelling of a rapidly fading electromagnetic transient in the galaxy NGC 4993, which is spatially coincident with GW170817 and with a weak, short γ-ray burst. The transient has physical parameters that broadly match the theoretical predictions of blue kilonovae from neutron-star mergers. The emitted electromagnetic radiation can be explained with an ejected mass of 0.04 ± 0.01 solar masses, with an opacity of less than 0.5 square centimetres per gram, at a velocity of 0.2 ± 0.1 times light speed. The power source is constrained to have a power-law slope of -1.2 ± 0.3, consistent with radioactive powering from r-process nuclides. (The r-process is a series of neutron capture reactions that synthesise many of the elements heavier than iron.) We identify line features in the spectra that are consistent with light r-process elements (atomic masses of 90-140). As it fades, the transient rapidly becomes red, and a higher-opacity, lanthanide-rich ejecta component may contribute to the emission. This indicates that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a nucleosynthetic source of the r-process elements.

2.
Med J Malaysia ; 78(1): 61-67, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36715193

RESUMO

INTRODUCTION: To evaluate the effectiveness of team-based self-directed learning (SDL) in the teaching of the undergraduate Year 5 surgical posting. MATERIALS AND METHODS: A quasi-experimental study was conducted to develop and administer a team-based SDL versus a conventional SDL to teach undergraduate surgical topics. One hundred and seventy-four medical students who underwent the Year 5 surgical posting were recruited. They were assigned to two groups receiving either the teambased SDL or the conventional SDL. Pre- and post-SDL assessments were conducted to determine students' understanding of selected surgical topics. A selfadministered questionnaire was used to collect student feedback on the team-based SDL. RESULTS: The team-based SDL group scored significantly higher than the conventional SDL group in the post-SDL assessment (74.70 ± 6.81 vs. 63.77 ± 4.18, t = -12.72, p < 0.01). The students agreed that the team-based SDL method facilitated their learning process. CONCLUSION: The study demonstrated that the use of a teambased SDL is an effective learning strategy for teaching the Year 5 surgical posting. This method encouraged peer discussion and promoted teamwork in completing task assignments to achieve the learning objectives.


Assuntos
Educação de Graduação em Medicina , Estudantes de Medicina , Humanos , Educação de Graduação em Medicina/métodos , Aprendizagem , Currículo , Avaliação Educacional
3.
BMC Public Health ; 22(1): 750, 2022 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-35422031

RESUMO

BACKGROUND: Testing is a foundational component of any COVID-19 management strategy; however, emerging evidence suggests that barriers and hesitancy to COVID-19 testing may affect uptake or participation and often these are multiple and intersecting factors that may vary across population groups. To this end, Health Canada's COVID-19 Testing and Screening Expert Advisory Panel commissioned this rapid review in January 2021 to explore the available evidence in this area. The aim of this rapid review was to identify barriers to COVID-19 testing and strategies used to mitigate these barriers. METHODS: Searches (completed January 8, 2021) were conducted in MEDLINE, Scopus, medRxiv/bioRxiv, Cochrane and online grey literature sources to identify publications that described barriers and strategies related to COVID-19 testing. RESULTS: From 1294 academic and 97 grey literature search results, 31 academic and 31 grey literature sources were included. Data were extracted from the relevant papers. The most cited barriers were cost of testing; low health literacy; low trust in the healthcare system; availability and accessibility of testing sites; and stigma and consequences of testing positive. Strategies to mitigate barriers to COVID-19 testing included: free testing; promoting awareness of importance to testing; presenting various testing options and types of testing centres (i.e., drive-thru, walk-up, home testing); providing transportation to testing centres; and offering support for self-isolation (e.g., salary support or housing). CONCLUSION: Various barriers to COVID-19 testing and strategies for mitigating these barriers were identified. Further research to test the efficacy of these strategies is needed to better support testing for COVID-19 by addressing testing hesitancy as part of the broader COVID-19 public health response.


Assuntos
Teste para COVID-19 , COVID-19 , COVID-19/diagnóstico , Humanos
4.
Med J Malaysia ; 77(1): 125-127, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35087013

RESUMO

A 60-year-old lady presented with lower abdominal discomfort and a huge palpable intra-abdominal mass for 4 months, with significant weight loss over half a year. Transvaginal ultrasonography and computed tomography (CT) abdomen showed a large right solid cystic mass likely ovarian in origin. The CA-125 was raised. With the provisional diagnosis of ovarian cancer patient underwent laparotomy at Hospital Umum Sarawak, Malaysia. However intraoperative findings showed that uterus and both ovaries were normal. The tumour was arising from the jejunum and adherent to the dome of the urinary bladder and right broad ligament. The tumour was resected and final diagnosis was jejunal gastrointestinal stromal tumour (GIST). We described this case which was misinterpreted as an ovarian cancer.


Assuntos
Tumores do Estroma Gastrointestinal , Neoplasias Ovarianas , Feminino , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Jejuno , Laparotomia , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Tomografia Computadorizada por Raios X
5.
Med J Malaysia ; 76(3): 432-435, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34031348

RESUMO

We present here a case of a 66-year-old lady who was diagnosed with right iliac fossa retroperitoneal leiomyosarcoma at Hospital Umum Sarawak. The challenge in this case was the extension of tumour with the involvement of her right ureter causing proximal hydroureter and hydronephrosis. After resection of tumour en-block with the involved segment of ureter, it was not possible to repair the ureteric defect directly. We used interpositional vascularized appendix graft to repair this large (7 cm) ureteric defect. We describe here this uncommon technique of ureter reconstruction.


Assuntos
Apêndice , Hidronefrose , Leiomiossarcoma , Procedimentos de Cirurgia Plástica , Ureter , Idoso , Feminino , Humanos , Leiomiossarcoma/diagnóstico por imagem , Leiomiossarcoma/cirurgia , Ureter/diagnóstico por imagem , Ureter/cirurgia
6.
Med J Malaysia ; 76(2): 138-144, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33742619

RESUMO

INTRODUCTION: Healthcare workers serve as the frontliners against the coronavirus 2019 disease (COVID-19) and this puts them most at risk of infection as they attend to numerous patients with unknown status. This study aimed to examine stress, anxiety, and depression among healthcare workers caring for COVID-19 patients in Sarawak General Hospital (SGH), Malaysia. MATERIALS AND METHODS: This cross-sectional observational study conducted in SGH during the pandemic with an online self-administered questionnaire composed of two parts, the socio-demographic characteristics, and the Depression Anxiety Stress Scale (DASS). RESULTS: A total of 105 healthcare workers responded to this study. A questionnaire in both Bahasa Melayu and English was used. The findings showed that all healthcare workers had mild anxiety, with the majority experiencing mild stress (57.1%), and almost half of the respondents experiencing mild depression (41%). Female subjects had a significant higher mean score in anxiety level and stress level compared to male subjects (10.0±3.20 vs. 8.6±2.93, p<0.05; 14.1±4.76 vs. 10.7±3.70, p<0.05, respectively). Staff who were transferred from other units to handle COVID-19 cases experienced more psychological symptoms. There were significant correlations between the depression, anxiety and stress levels among the healthcare workers and the number of children they had (r=0.739, p=0.001; r=0.642, p=0.001; r=1, p =0.001 respectively). However, the stress level among the healthcare workers was reversely correlated with their years of working experience (r=-0.199, p=0.042). CONCLUSION: This study identified some socio-demographic factors associated with increased levels of stress, anxiety and depression among the healthcare workers during pandemic, which may lay ground for future interventions.


Assuntos
Ansiedade/epidemiologia , COVID-19/psicologia , COVID-19/terapia , Depressão/epidemiologia , Pessoal de Saúde/psicologia , Estresse Psicológico/epidemiologia , Adulto , Estudos Transversais , Feminino , Humanos , Malásia , Masculino , Fatores Socioeconômicos , Inquéritos e Questionários
7.
Osteoporos Int ; 31(12): 2345-2354, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32632509

RESUMO

The risks for hip fracture and vertebral fracture, but not the risk for distal radius fracture, were significantly higher in the blindness group than in the control group with a maximum 12-year follow-up. PURPOSE: To evaluate the influence of visual impairment on the risk for osteoporotic fractures at common sites: hip, thoracic/lumbar vertebra, and distal radius. METHODS: This longitudinal follow-up study used a database of a national sample cohort from 2002 to 2013 provided by the Korean National Health Insurance Service. Of a total of 1,125,691 subjects, 3918 patients with visual impairment and age ≥ 50 years were enrolled in a 1:4 ratio; 15,672 control participants were matched for age, sex, income, and region of residence. Stratified Cox proportional-hazards models were used to evaluate the crude and adjusted (for steroid medication, rheumatoid arthritis, depression, osteoporosis, diabetes mellitus, and stroke history) hazard ratios (HRs) for each fracture site. Fracture diagnoses were based on the ICD-10 codes: hip fracture (S720, S721, S722), vertebral fracture (S220, S320), and distal radius fracture (S525). RESULTS: The HRs for hip and vertebral fracture were significantly higher in the blindness group (adjusted HR = 2.46, p < 0.001 for hip fracture; adjusted HR = 1.42, p = 0.020 for thoracic/lumbar vertebral fracture) than in the matched control group. However, the HR for distal radius fracture was not higher in the blindness group. The HRs for all three fracture sites were not significantly higher in the non-blindness visual impairment group after adjustment. CONCLUSION: The risks for hip fracture and vertebral fracture were significantly higher in the blindness group. However, the risk for distal radius fracture was not related to visual impairment including blindness.


Assuntos
Fraturas do Quadril , Fraturas por Osteoporose , Fraturas do Rádio , Fraturas da Coluna Vertebral , Cegueira , Seguimentos , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/etiologia , Humanos , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Fraturas do Rádio/epidemiologia , Fatores de Risco , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia
8.
Qual Health Res ; 30(11): 1737-1748, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32452301

RESUMO

Breastfeeding is represented to support healthy body weight and food security. However, breastfeeding may be negatively impacted by high maternal body weight and income-related food insecurity. Guided by feminist poststructural methodology, this study explored breastfeeding beliefs and practices among women from Nova Scotia, Canada, identifying as income-related food insecure and overweight. Participants who were pregnant for the first time and intending to breastfeed participated in three interviews: prenatal (n = 8), first month postpartum (n = 6), and 3 months postpartum (n = 6). Employing discourse analyses, we found that participants' experiences aligned with dominant discursive representations of these health issues, informed through normative understandings of what it means to mother. However, some participants resisted and reframed what constitutes good mothering to identify with maternal subjectivities that were context specific. The findings have implications for understanding how discourses shape maternal identities and their effects for breastfeeding and other health-related practices.


Assuntos
Aleitamento Materno , Mães , Feminino , Humanos , Nova Escócia , Sobrepeso , Pobreza , Gravidez
9.
Med J Malaysia ; 75(5): 606-608, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32918439

RESUMO

Ileo-ileal knotting is a rare cause of intestinal obstruction. In this condition, one bowel loop makes a knot with an adjacent bowel loop, resulting in mechanical obstruction and even gangrene of the bowel. We present a case of a young girl with ileo-ileal knotting resulting in a closed-loop obstruction and gangrene of the small bowel loop. This is a difficult condition to diagnose; a high index of suspicion and early surgical intervention are essential to reduce morbidity and mortality.


Assuntos
Obstrução Intestinal/diagnóstico , Intestino Delgado/fisiopatologia , Intestino Delgado/cirurgia , Adolescente , Feminino , Gangrena/etiologia , Humanos , Obstrução Intestinal/complicações , Obstrução Intestinal/cirurgia , Procedimentos de Cirurgia Plástica , Procedimentos Cirúrgicos Operatórios/métodos , Resultado do Tratamento
10.
Med J Malaysia ; 75(1): 38-42, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32008018

RESUMO

INTRODUCTION: Cerebral venous sinus thrombosis (CVST) is a potentially fatal neurological condition. However, due to the non-specific clinical and radiological features of CVST, it can sometimes result in a delay in the diagnosis and subsequent management. The aim of this study was to evaluate the demography, risk factors and one-year outcome of CVST patients treated in Hospital Universiti Sains Malaysia. METHODS: In this retrospective study, we reviewed the cases diagnosed with CVST admitted to our centre from January 2011 until November 2015. RESULTS: A total of 15 patients were included in this review. The patterns of imaging findings as well as risk factors for CVST is discussed with a review of the literature and current management practices. One year followed-up showed full recovery (Glasgow Outcome Scale (GOS) of 5) in 10 cases (66.7%), whereas 4 cases (26.7%) with GOS of 4 (three cases with neurological deficits, and 1 case with mild symptom. There was one case of mortality in this study secondary to sepsis during hospitalisation. The presenting symptoms were mainly headache, focal neurology deficits, seizure and altered sensorium. Risk factors identified were oral contraceptive pills usage, chronic sinuses or ear infections, and obesity. Initial computed tomography (CT) scan showed various findings and haemorrhagic infarct was one of the common findings. Magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) revealed majority of the patients had occlusion at two or more venous sinus sites. No patients had new or recurrent intracranial haemorrhage following initiation of anticoagulation therapy. CONCLUSION: Thus it is considerable safe to start anticoagulation therapy in CVST patients including those with intracranial haemorrhage. We propose further neuroimaging to avoid missed diagnosis of CVST in patient presented with recent onset headache and CT evidence of unusual cerebral infarction.


Assuntos
Trombose dos Seios Intracranianos/diagnóstico , Trombose dos Seios Intracranianos/tratamento farmacológico , Adolescente , Adulto , Anticoagulantes/administração & dosagem , Feminino , Humanos , Malásia , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Fatores de Risco , Trombose dos Seios Intracranianos/etiologia , Adulto Jovem
11.
Insect Mol Biol ; 28(2): 277-289, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30422347

RESUMO

Tephritid fruit flies are destructive agricultural pests that are the targets of expensive population eradication and suppression efforts. Genetic pest management is one of the strategies for reducing or eliminating tephritid populations, relying upon the genetic manipulation of insects to render them sterile or capable of transmitting deleterious traits through gene drive. Currently, radiation, chemical mutagenesis, and transgenic techniques are employed to generate agents for genetic pest management, but new methods must be explored and developed for all tephritid pest species. Targeted mutagenesis induced by nonhomologous end join repair of clustered regularly interspaced short palindromic repeats and the CRISPR associated protein 9 (Cas9) (commonly known as CRISPR/Cas9) has been demonstrated to be an efficient method for creating knock-out mutants and can be utilized to create germline mutations in Tephritidae. In this paper, we describe detailed methods to knockout the white gene in three tephritid species in the genera Anastrepha, Bactrocera and Ceratitis, including the first demonstration of CRISPR/Cas9 induced mutations in the genus Anastrepha. Lastly, we discuss the variables in tephritid systems that directed method development as well as recommendations for performing injections in remote containment facilities with little molecular biology capabilities. These methods and recommendations combined can serve as a guide for others to use in pursuit of developing CRISPR/Cas9 methods in tephritid systems.


Assuntos
Sistemas CRISPR-Cas , Técnicas de Inativação de Genes , Tephritidae/genética , Animais , Mutação
12.
Nature ; 502(7471): 346-9, 2013 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-24132291

RESUMO

Super-luminous supernovae that radiate more than 10(44) ergs per second at their peak luminosity have recently been discovered in faint galaxies at redshifts of 0.1-4. Some evolve slowly, resembling models of 'pair-instability' supernovae. Such models involve stars with original masses 140-260 times that of the Sun that now have carbon-oxygen cores of 65-130 solar masses. In these stars, the photons that prevent gravitational collapse are converted to electron-positron pairs, causing rapid contraction and thermonuclear explosions. Many solar masses of (56)Ni are synthesized; this isotope decays to (56)Fe via (56)Co, powering bright light curves. Such massive progenitors are expected to have formed from metal-poor gas in the early Universe. Recently, supernova 2007bi in a galaxy at redshift 0.127 (about 12 billion years after the Big Bang) with a metallicity one-third that of the Sun was observed to look like a fading pair-instability supernova. Here we report observations of two slow-to-fade super-luminous supernovae that show relatively fast rise times and blue colours, which are incompatible with pair-instability models. Their late-time light-curve and spectral similarities to supernova 2007bi call the nature of that event into question. Our early spectra closely resemble typical fast-declining super-luminous supernovae, which are not powered by radioactivity. Modelling our observations with 10-16 solar masses of magnetar-energized ejecta demonstrates the possibility of a common explosion mechanism. The lack of unambiguous nearby pair-instability events suggests that their local rate of occurrence is less than 6 × 10(-6) times that of the core-collapse rate.

14.
Med J Malaysia ; 74(1): 87-89, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30846670

RESUMO

Large intracranial tumour may present only with psychiatric symptoms without any neurological deficits. Delay in surgical treatment may significantly affect the quality of life in these patients. We report a case of a young engineering student who was diagnosed as treatment-resistant depression without initial neuroimaging study. Further neuroimaging studies revealed he has a large falcine meningioma. His psychiatric symptoms resolved following surgical resection of the tumour. We emphasized the importance of initial neuroimaging study in young patients presenting with psychiatric symptoms.


Assuntos
Transtorno Depressivo Resistente a Tratamento/etiologia , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Adulto , Dura-Máter , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/psicologia , Meningioma/complicações , Meningioma/diagnóstico por imagem , Meningioma/psicologia , Neuroimagem
15.
Med J Malaysia ; 74(4): 338-340, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31424046

RESUMO

We reported a case of cauda equina myxopapillary ependymoma in a patient who presented with atypical history of progressive blurring of vision. Ophthalmology examination revealed relative afferent pupillary defect, binasal hemianopia and papilloedema. This case report serves as a reminder that the intraspinal tumour could be a cause of papilloedema, despite rare, should be considered in a hydrocephalus patient who presented with no intracranial pathology and minimal spinal symptoms.


Assuntos
Cauda Equina , Ependimoma/diagnóstico , Hidrocefalia/etiologia , Papiledema/etiologia , Neoplasias do Sistema Nervoso Periférico/diagnóstico , Adulto , Ependimoma/complicações , Humanos , Hidrocefalia/diagnóstico , Masculino , Papiledema/diagnóstico , Neoplasias do Sistema Nervoso Periférico/complicações
16.
Clin Exp Immunol ; 194(1): 125-136, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30022471

RESUMO

Although patients with diabetes contract infectious diseases at higher frequencies, and in more severe forms, compared to non-diabetics, the underlying defects of the immune function have not been defined clearly. To address this, we designed an immune monitoring protocol and analysed the functional status of various immune cells. Peripheral blood mononuclear cells (PBMCs) were stimulated with the proper ligands and the functional reactivity of each lineage of cells was subsequently measured. Patients with type 2 diabetes mellitus (T2DM) had PBMC composition ratios comparable to healthy controls, except for a higher frequency of B cell and effector T cell fractions. The capacity of myeloid cells to secrete proinflammatory cytokines was not diminished in terms of the sensitivity and magnitude of the response. Furthermore, cytolytic activity and interferon (IFN)-γ production of natural killer (NK) cells and CD8+ T cells were not decreased in T2DM patients. Phenotypical maturation of dendritic cells, indicated by the up-regulation of major histocompatibility complex (MHC) proteins and co-stimulatory molecules in response to lipopolysaccharide (LPS), was slightly enhanced in T2DM patients. Finally, the functional differentiation profiles of CD4+ T cells did not differ between T2DM patients and the control group. These data indicate that patients with long-lasting T2DM do not have any gross functional defects in immune cells, at least in circulating monocytes, dendritic cells, NK cells and T lymphocytes.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Diabetes Mellitus Tipo 2/imunologia , Células Matadoras Naturais/imunologia , Leucócitos Mononucleares/imunologia , Idoso , Citocinas/metabolismo , Células Dendríticas/citologia , Feminino , Humanos , Interferon gama/metabolismo , Ativação Linfocitária/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade
17.
Osteoarthritis Cartilage ; 26(3): 405-413, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29229562

RESUMO

OBJECTIVE: To evaluate cross-correlations of ex vivo electromechanical properties with cartilage and subchondral bone plate thickness, as well as their sensitivity and specificity regarding early cartilage degeneration in human tibial plateau. METHOD: Six pairs of tibial plateaus were assessed ex vivo using an electromechanical probe (Arthro-BST) which measures a quantitative parameter (QP) reflecting articular cartilage compression-induced streaming potentials. Cartilage thickness was then measured with an automated thickness mapping technique using Mach-1 multiaxial mechanical tester. Subsequently, a visual assessment was performed by an experienced orthopedic surgeon using the International Cartilage Repair Society (ICRS) grading system. Each tibial plateau was finally evaluated with µCT scanner to determine the subchondral-bone plate thickness over the entire surface. RESULTS: Cross-correlations between assessments decreased with increasing degeneration level. Moreover, electromechanical QP and subchondral-bone plate thickness increased strongly with ICRS grade (ρ = 0.86 and ρ = 0.54 respectively), while cartilage thickness slightly increased (ρ = 0.27). Sensitivity and specificity analysis revealed that the electromechanical QP is the most performant to distinguish between different early degeneration stages, followed by subchondral-bone plate thickness and then cartilage thickness. Lastly, effect sizes of cartilage and subchondral-bone properties were established to evaluate whether cartilage or bone showed the most noticeable changes between normal (ICRS 0) and each early degenerative stage. Thus, the effect sizes of cartilage electromechanical QP were almost twice those of the subchondral-bone plate thickness, indicating greater sensitivity of electromechanical measurements to detect early osteoarthritis. CONCLUSION: The potential of electromechanical properties for the diagnosis of early human cartilage degeneration was highlighted and supported by cartilage thickness and µCT assessments.


Assuntos
Cartilagem Articular/fisiopatologia , Osteoartrite/fisiopatologia , Idoso , Doenças Assintomáticas , Fenômenos Biomecânicos , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Humanos , Pessoa de Meia-Idade , Osteoartrite/diagnóstico por imagem , Tíbia , Microtomografia por Raio-X
18.
Mol Psychiatry ; 22(8): 1155-1163, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27895323

RESUMO

The polymorphic CYP2C19 enzyme metabolizes psychoactive compounds and is expressed in the adult liver and fetal brain. Previously, we demonstrated that the absence of CYP2C19 is associated with lower levels of depressive symptoms in 1472 Swedes. Conversely, transgenic mice carrying the human CYP2C19 gene (2C19TG) have shown an anxious phenotype and decrease in hippocampal volume and adult neurogenesis. The aims of this study were to: (1) examine whether the 2C19TG findings could be translated to humans, (2) evaluate the usefulness of the 2C19TG strain as a tool for preclinical screening of new antidepressants and (3) provide an insight into the molecular underpinnings of the 2C19TG phenotype. In humans, we found that the absence of CYP2C19 was associated with a bilateral hippocampal volume increase in two independent healthy cohorts (N=386 and 1032) and a lower prevalence of major depressive disorder and depression severity in African-Americans (N=3848). Moreover, genetically determined high CYP2C19 enzymatic capacity was associated with higher suicidality in depressed suicide attempters (N=209). 2C19TG mice showed high stress sensitivity, impaired hippocampal Bdnf homeostasis in stress, and more despair-like behavior in the forced swim test (FST). After the treatment with citalopram and 5-HT1A receptor agonist 8OH-DPAT, the reduction in immobility time in the FST was more pronounced in 2C19TG mice compared with WTs. Conversely, in the 2C19TG hippocampus, metabolic turnover of serotonin was reduced, whereas ERK1/2 and GSK3ß phosphorylation was increased. Altogether, this study indicates that elevated CYP2C19 expression is associated with depressive symptoms, reduced hippocampal volume and impairment of hippocampal serotonin and BDNF homeostasis.


Assuntos
Transtornos de Ansiedade/genética , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C19/metabolismo , Negro ou Afro-Americano/genética , Animais , Ansiedade/diagnóstico por imagem , Ansiedade/genética , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Citalopram/farmacologia , Citocromo P-450 CYP2C19/efeitos dos fármacos , Depressão/tratamento farmacológico , Depressão/genética , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/metabolismo , Hipocampo/metabolismo , Homeostase/genética , Homeostase/fisiologia , Humanos , Camundongos , Camundongos Transgênicos , Neurogênese/genética , Receptor 5-HT1A de Serotonina/metabolismo , Serotonina/metabolismo , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia
20.
Analyst ; 143(4): 936-942, 2018 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-29363681

RESUMO

The objective of this study is to develop an accurate, rapid, simple, and label-free assay technology that enables point-of-care diagnosis of AIDS. For this, 3-dimensional (3D) probes to sensitively detect anti-HIV antibodies were designed and synthesized by genetically presenting a HIV antigen (gp41) on the surface of engineered human ferritin nanoparticles. The 3D probes also present multi-copies of the hexa-histidine peptide (H6) on their surface to chemisorb gold ions (Au3+), which is essential for the generation and self-enhancement of assay signals. The developed new assay technology (named "one-step-immunoassay") quickly produced clear optical signals through a simple and convenient one-step procedure. The diagnostic performance of the one-step-immunoassay was compared with that of the conventional lateral flow assay (LFA) using 30 AIDS patient and 20 healthy sera. The sensitivity of LFA was only 63% when a single antigen (gp41) was used but enhanced to 90% when three different antigens (gp41, p24, and gp120) were used together as the assay probes. In contrast, the one-step-immunoassay using only gp41 produced strong optical signals within 15 min without causing any false negative/positive signals, showing 100% sensitivity and 100% specificity and holding promising potential for clinical point-of-care diagnosis of AIDS.


Assuntos
Síndrome da Imunodeficiência Adquirida/diagnóstico , Anticorpos Anti-HIV/análise , Imunoensaio , Sistemas Automatizados de Assistência Junto ao Leito , Proteína gp41 do Envelope de HIV/análise , Humanos , Sensibilidade e Especificidade
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