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INTRODUCTION: High-fidelity simulation (HFS) provides a high level of interactivity and realistic experience for the learner by means of using full scale computerised patient simulators. It imitates clinical experience in a controlled and safe environment that closely resembles reality. The purpose of this study was to compare the efficacy of HFS versus video-assisted lecture (VAL) based education in enhancing and consolidating retention of skills among undergraduate medical students. MATERIALS AND METHODS: A randomised controlled trial (RCT) study involving 111 undergraduate medical students was conducted where the competency of skills was assessed by objective structured clinical examination (OSCE) in the first, fourth and seventh/eighth weeks. A cohort of 12-14 students was enrolled for each session. The randomisation of the participants into control (VAL-based teaching) and intervention (HFS-based teaching) groups was achieved by implementing the computer-based random sequence generation method. VAL-based teaching module was a fully interactive face-to-face teaching session where a prerecorded video clip was used. The video clip detailed the diagnosis of tension pneumothorax in an acute medical emergency and its management by performing needle decompression on a high-fidelity patient simulator (METIman). HFS-based teaching module was delivered as a fully interactive hands-on training session conducted on the same METIman to demonstrate the diagnosis of tension pneumothorax in an acute medical emergency and its management by performing needle decompression. OSCE scores were compared as the denominator of learning (enhancement and retention of skills) between two groups who underwent training with either VAL-based or HFS-based teachings. The OSCE assessments were used to evaluate the participants' performance as a group. These scores were used to compare the enhancement and medium-term retention of skills between the groups. The outcome was measured with the mean and standard deviation (SD) for the total OSCE scores for skills assessments. We used General Linear Model two-way mixed ANOVA to ascertain the difference of OSCE marks over assessment time points between the control and the intervention groups. ANCOVA and two-way mixed ANOVA were used to calculate the effect size and the partial Eta squared. p value less than 0.05 was taken to be statistically significant. RESULTS: The two-way mixed ANOVA showed no statistically significant difference in mean OSCE scores between intervention and control groups (p=0.890), although the mean score of the intervention group was better than the control group. CONCLUSION: Our study demonstrated that HFS was not significantly effective over VAL-based education in enhancing skills and consolidating retention among undergraduate medical students. Further research is needed to determine its suitability for inclusion in the course curriculum considering the cost-effectiveness of implementing HFS that may supplement traditional teaching methods.
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Competência Clínica , Educação de Graduação em Medicina , Humanos , Educação de Graduação em Medicina/métodos , Feminino , Masculino , Estudantes de Medicina , Treinamento com Simulação de Alta Fidelidade/métodos , Avaliação Educacional , Adulto Jovem , AdultoRESUMO
BACKGROUND: Multiple vaccine platforms against COVID-19 have been developed and found safe and efficacious at a record speed. Although most are effective, they vary in their ease of production and distribution, their potential speed of modification against new variants, and their durability of protection and safety in certain target groups. SOURCES OF DATA: Our discussion is based on published reports of clinical trials and analyses from national and global health agencies. AREAS OF AGREEMENT: The production of neutralizing antibodies against the viral spike protein is protective, and all vaccines for which published data exist have been found to be effective against severe disease caused by the viral strain they target. AREAS OF CONTROVERSY: The degree to which vaccines protect against emerging variants, moderate disease and asymptomatic infection remains somewhat unclear. GROWING POINTS: Knowledge of the duration of protection and its decay is increasing, and discussions of booster frequency and target strains are ongoing. AREAS TIMELY FOR DEVELOPING RESEARCH: The global effort to combat transmission and disease continues to rely upon intense epidemiological surveillance, whilst real-world data and clinical trials shape vaccination schedules and formulae.
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COVID-19 , Vacinas , Humanos , Vacinas contra COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controleRESUMO
We assessed two electronic search tools that screen medical records for documented fractures. Both programs reliably identified patients with any fracture but missed individuals with minimal trauma fracture to different degrees. A hybrid tool combining the methodology of both tools is likely to improve the identification of those with osteoporosis. PURPOSE: Most patients who suffer a minimal trauma fracture remain undiagnosed, placing them at high risk of refracture. Case finding can be improved by electronic search tools that screen medical records for documented fractures. Here, we assessed the efficacy of two new programs, AES and XRAIT, in identifying patients with minimal trauma fracture. METHODS: Each tool was applied to search the electronic medical record and/or radiology reports at two tertiary hospitals in Sydney, Australia, from 1 July to 31 December 2018. Samples of the extracted reports were then manually reviewed to determine the sensitivity of each program in detecting minimal trauma fractures. RESULTS: At the two centers, AES detected 872 and 1364 cases, whereas XRAIT identified 1414 and 2180 patients with fractures, respectively. The true positive rate for "any fracture" was similar for both instruments (77-88%). However, the ability to detect "minimal trauma fractures" differed between programs and centers (53-75% accuracy), with each tool identifying separate subsets of patients. Concordance between both tools was less than half of the combined total number of minimal trauma fractures (43-45%). Considering the total number of minimal trauma fractures detected by both tools combined, AES correctly identified 52-55% of cases while XRAIT identified 88-93% of cases. CONCLUSION: Both programs reliably identified patients with any fracture but missed individuals with minimal trauma fracture to different degrees. Hybrid tools combining the methodology of XRAIT and AES are likely to improve the identification of patients who require investigation and treatment for osteoporosis.
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Osteoporose , Fraturas por Osteoporose , Atenção à Saúde , Registros Eletrônicos de Saúde , Eletrônica , Humanos , Fraturas por Osteoporose/diagnóstico , Fraturas por Osteoporose/etiologiaRESUMO
Significant sleep disturbance can occur following major abdominal surgery. We aimed to evaluate the effectiveness of earplugs and eye masks in improving sleep quality and patient satisfaction, reducing nursing demands and in the incidence of delirium in patients after major abdominal surgery. We conducted a randomised controlled trial in 100 patients undergoing major abdominal surgery. We randomly allocated participants to sleep with or without earplugs and eye masks on postoperative days 1-3. The primary outcome measure was sleep quality as measured by the Richards-Campbell Sleep Questionnaire. Secondary outcomes were patient satisfaction, frequency of nursing demand and incidence of delirium measured by the Neelon and Champagne Confusion Scale. Median (IQR [range]) sleep scores were 64 (38-74 [0-100] and 60 (44-82 [18-100]) for the control and intervention groups, respectively (p = 0.310). Age and Pittsburgh Sleep Quality Index scores were found to be significant factors affecting sleep quality. There were no differences in patient satisfaction, reduction in frequency of nursing demands or incidence of delirium on postoperative days 1-3 after major abdominal surgery. The compliance rate in the intervention group was 60-65%. This study has demonstrated that the use of earplugs and eye masks did not contribute to improvements in sleep quality. Of note, sleep quality was moderate, with higher age and worse baseline sleep quality contributing to worse sleep scores. More studies are needed to investigate interventions to improve sleep quality after major abdominal surgery.
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Abdome/cirurgia , Dispositivos de Proteção das Orelhas , Dispositivos de Proteção dos Olhos , Sono/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Período Pós-Operatório , Estudos Prospectivos , Método Simples-Cego , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: To determine the carrier frequency and common mutations of Mendelian variants in Chinese couples using next-generation sequencing (NGS). METHODS: Preconception expanded carrier testing using NGS was offered to women who attended the subfertility clinic. The test was then offered to the partners of women who had positive screening results. Carrier frequency was calculated, and the results of the NGS panel were compared with those of a target panel. RESULTS: One hundred twenty-three women and 20 of their partners were screened. Overall, 84 (58.7%) individuals were identified to be carriers of at least one disease, and 68 (47.6%) were carriers after excluding thalassaemias. The most common diseases found were GJB2-related DFNB1 nonsyndromic hearing loss and deafness (1 in 4), alpha-thalassaemia (1 in 7), beta-thalassaemia (1 in 14), 21-hydroxylase deficient congenital adrenal hyperplasia (1 in 13), Pendred's syndrome (1 in 36), Krabbe's disease (1 in 48), and spinal muscular atrophy (1 in 48). Of the 43 identified variants, 29 (67.4%) were not included in the American College of Medical Genetics and Genomics or American College of Obstetrics and Gynecology guidelines. Excluding three couples with alpha-thalassaemia, six at-risk couples were identified. CONCLUSION: The carrier frequency of the investigated members of the Chinese population was 58.7% overall and 47.6% after excluding thalassaemias. This frequency is higher than previously reported. Expanded carrier screening using NGS should be provided to Chinese people to improve the detection rate of carrier status and allow optimal pregnancy planning.
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Povo Asiático , Sequenciamento de Nucleotídeos em Larga Escala , Povo Asiático/genética , Feminino , Triagem de Portadores Genéticos , Hong Kong/epidemiologia , Humanos , Mutação , Projetos Piloto , GravidezRESUMO
A novel heterogeneous catalyst, the ionic liquid (IL) of 1-butyl-3-methylimidazolium acetate (BmimOAc) immobilized on MIL-101-NH2, denoted as IL(OAc-)-MIL-101-NH2, was prepared by the "ship-in-a-bottle" strategy. The IL of BmimOAc was prepared in the MIL-101-NH2 nanocages primordially, in which the condensation product of MIL-101-NH2's amine group with 1,1'-carbonyldiimidazole (CDI) reacted with 1-bromo butane, and then the intermediate exchanged with potassium acetate. The structure and physicochemical properties of IL(OAc-)-MIL-101-NH2 were characterized by powder X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, DRS UV-vis, nitrogen adsorption-desorption, and elemental analysis. The results indicated that BmimOAc was anchored in the MIL-101-NH2 skeleton via the acylamino group and confined in the nanocages in the form of a single molecule. The composite material of IL(OAc-)-MIL-101-NH2 exhibited excellent catalytic activity and catalytically synthesized 3-aryl-2-oxazolone in an excellent yield of 92%. It can be reused up to six times without noteworthy loss of its activity and demonstrated distinct size-selective property for substrates. It was conjectured that the diffusion kinetics of reactants could be controlled by the aperture size of the metal-organic framework support.
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Lower limb cellulitis is a common cause for hospital admissions. In this retrospective study, we assessed the characteristics and outcome of patients admitted in an acute medical unit. The mean duration of treatment was 10.48 days, with 95.5% receiving antibiotics for more than 5 days. Mean length of stay (LOS) was 5.19 days. 12-month readmission rate was higher in patients with diabetes, chronic kidney disease (CKD) and previous stroke. Diabetes, CKD, previous stroke, and elevated procalcitonin levels were independently associated with prolonged admission (>3 days).
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Spinal networks in the cervical and lumbar cord are actively coupled during locomotion to coordinate arm and leg activity. The goals of this project were to investigate the intersegmental cervicolumbar connectivity during cycling after incomplete spinal cord injury (iSCI) and to assess the effect of rehabilitation training on improving reflex modulation mediated by cervicolumbar pathways. Two studies were conducted. In the first, 22 neurologically intact (NI) people and 10 people with chronic iSCI were recruited. The change in H-reflex amplitude in flexor carpi radialis (FCR) during leg cycling and H-reflex amplitude in soleus (SOL) during arm cycling were investigated. In the second study, two groups of participants with chronic iSCI underwent 12 wk of cycling training: one performed combined arm and leg cycling (A&L) and the other legs only cycling (Leg). The effect of training paradigm on the amplitude of the SOL H-reflex was assessed. Significant reduction in the amplitude of both FCR and SOL H-reflexes during dynamic cycling of the opposite limbs was found in NI participants but not in participants with iSCI. Nonetheless, there was a significant reduction in the SOL H-reflex during dynamic arm cycling in iSCI participants after training. Substantial improvements in SOL H-reflex properties were found in the A&L group after training. The results demonstrate that cervicolumbar modulation during rhythmic movements is disrupted in people with chronic iSCI; however, this modulation is restored after cycling training. Furthermore, involvement of the arms simultaneously with the legs during training may better regulate the leg spinal reflexes. NEW & NOTEWORTHY This work systematically demonstrates the disruptive effect of incomplete spinal cord injury on cervicolumbar coupling during rhythmic locomotor movements. It also shows that the impaired cervicolumbar coupling could be significantly restored after cycling training. Actively engaging the arms in rehabilitation paradigms for the improvement of walking substantially regulates the excitability of the lumbar spinal networks. The resulting regulation may be better than that obtained by interventions that focus on training of the legs only.
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Exercício Físico , Reflexo H , Traumatismos da Medula Espinal/fisiopatologia , Medula Espinal/fisiopatologia , Adulto , Dorso/fisiopatologia , Feminino , Humanos , Masculino , Pescoço/fisiopatologiaRESUMO
Because electric vehicles (EVs) are used intermittently with long resting periods in the fully charged state before driving, calendar aging behavior is an important criterion for the application of Li-ion batteries used in EVs. In this work, Ni-rich Li[Nix Coy Mn1 -x-y ]O2 (x = 0.8 and 0.9) cathode materials with high energy densities, but low cycling stabilities are investigated to characterize their microstructural degradation during accelerated calendar aging. Although the particles seem to maintain their crystal structures and morphologies, the microcracks which develop during calendar aging remain even in the fully discharged state. An NiO-like phase rock-salt structure of tens of nanometers in thickness accumulates on the surfaces of the primary particles through parasitic reactions with the electrolyte. In addition, the passive layer of this rock-salt structure near the microcracks is gradually exfoliated from the primary particles, exposing fresh surfaces containing Ni4+ to the electrolyte. Interestingly, the interior primary particles near the microcracks have deteriorated more severely than the outer particles. The microstructural degradation is worsened with increasing Ni contents in the cathode materials, directly affecting electrochemical performances such as the reversible capacities and voltage profiles.
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The spinal cervico-lumbar interaction during rhythmic movements in humans has recently been studied; however, the role of arm movements in modulating the corticospinal drive to the legs is not well understood. The goals of this study were to investigate the effect of active rhythmic arm movements on the corticospinal drive to the legs (study 1) and assess the effect of simultaneous arm and leg training on the corticospinal pathway after incomplete spinal cord injury (iSCI) (study 2). In study 1, neurologically intact (NI) participants or participants with iSCI performed combinations of stationary and rhythmic cycling of the arms and legs while motor evoked potentials (MEPs) were recorded from the vastus lateralis (VL) muscle. In the NI group, arm cycling alone could facilitate the VL MEP amplitude, suggesting that dynamic arm movements strongly modulate the corticospinal pathway to the legs. No significant difference in VL MEP between conditions was found in participants with iSCI. In study 2, participants with iSCI underwent 12 wk of electrical stimulation-assisted cycling training: one group performed simultaneous arm and leg (A&L) cycling and the other legs-only cycling. MEPs in the tibialis anterior (TA) muscle were compared before and after training. After training, only the A&L group had a significantly larger TA MEP, suggesting increased excitability in the corticospinal pathway. The findings demonstrate the importance of arm movements in modulating the corticospinal drive to the legs and suggest that active engagement of the arms in lower limb rehabilitation may produce better neural regulation and restoration of function.NEW & NOTEWORTHY This study aimed to demonstrate the importance of arm movements in modulating the corticospinal drive to the legs. It provides direct evidence in humans that active movement of the arms could facilitate corticospinal transmission to the legs and, for the first time, shows that facilitation is absent after spinal cord injury. Active engagement of the arms in lower limb rehabilitation increased the excitability of the corticospinal pathway and may produce more effective improvement in leg function.
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Exercício Físico , Tratos Piramidais/fisiopatologia , Músculo Quadríceps/inervação , Traumatismos da Medula Espinal/fisiopatologia , Adulto , Braço/inervação , Estudos de Casos e Controles , Potencial Evocado Motor , Feminino , Humanos , Perna (Membro)/inervação , Masculino , Pessoa de Meia-Idade , Músculo Quadríceps/fisiopatologiaRESUMO
BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disease in the elderly and is associated with increased mortality. The extent of multimorbidity in patients with BP and its impact on survival are unclear. OBJECTIVES: To describe the extent and spectrum of multimorbidity in patients with BP and to ascertain its impact on survival. METHODOLOGY: This was a case-control study conducted in the setting of an academic medical centre. Cases defined as newly diagnosed BP patients referred to the inpatient dermatology service between 2005 and 2014. For every case, three age- and gender-matched controls were randomly selected. Retrospective review of medical records was performed. Univariate and multivariate comparisons of cases and controls were performed using conditional logistic regression. RESULTS: A total of 105 cases and 315 controls were included in this study. Eighty-eight cases (84%) were multimorbid (≥2 chronic diseases) as compared to 205 controls (65%) (P < 0.001), while the mean number of comorbid conditions was 3.2 ± 1.6 in cases compared to 2.4 ± 1.6 in controls (P < 0.001). 43% of cases had ≥4 comorbidities compared to 27% in controls (P = 0.003). On multivariate analysis (adjusting for age, gender and comorbidities), neurological disease (OR 10.93; CI: 5.74, 20.79) and hypertension (OR 2.38; CI: 1.18, 4.77) were positively associated with BP. Charlson comorbidity index was 6.0 ± 2.5 in cases compared to 5.0 ± 2.1 in controls (P = 0.002), and the 1-year mortality of cases and controls was 32.4% and 17.8%, respectively. CONCLUSION: Our study has shown that a significant proportion of patients with BP are multimorbid and individually have a higher number of comorbidities compared to matched controls. Disease burden and multimorbidity may well impact the prognosis of patients with BP.
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Multimorbidade , Penfigoide Bolhoso/complicações , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Análise de SobrevidaRESUMO
INTRODUCTION: No universal expanded newborn screening service for inborn errors of metabolism is available in Hong Kong despite its long history in developed western countries and rapid development in neighbouring Asian countries. To increase the local awareness and preparedness, the Centre of Inborn Errors of Metabolism of the Chinese University of Hong Kong started a private inborn errors of metabolism screening programme in July 2013. This study aimed to describe the results and implementation of this screening programme. METHODS: We retrieved the demographics of the screened newborns and the screening results from July 2013 to July 2016. These data were used to calculate quality metrics such as call-back rate and false-positive rate. Clinical details of true-positive and false-negative cases and their outcomes were described. Finally, the call-back logistics for newborns with positive screening results were reviewed. RESULTS: During the study period, 30 448 newborns referred from 13 private and public units were screened. Of the samples, 98.3% were collected within 7 days of life. The overall call-back rate was 0.128% (39/30 448) and the false-positive rate was 0.105% (32/30 448). Six neonates were confirmed to have inborn errors of metabolism, including two cases of medium-chain acyl-coenzyme A dehydrogenase deficiency, one case of carnitine-acylcarnitine translocase deficiency, and three milder conditions. One case of maternal carnitine uptake defect was diagnosed. All patients remained asymptomatic at their last follow-up. CONCLUSION: The Centre of Inborn Errors of Metabolism has established a comprehensive expanded newborn screening programme for selected inborn errors of metabolism. It sets a standard against which the performance of other private newborn screening tests can be compared. Our experience can also serve as a reference for policymakers when they contemplate establishing a government-funded universal expanded newborn screening programme in the future.
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Erros Inatos do Metabolismo/diagnóstico , Triagem Neonatal/organização & administração , Avaliação de Processos e Resultados em Cuidados de Saúde , Serviços de Saúde da Criança/organização & administração , Reações Falso-Positivas , Feminino , Hong Kong , Humanos , Recém-Nascido , MasculinoRESUMO
Introduction: Fragile X syndrome (FXS) is a genetically determined developmental disorder. Underlying genotype is cytosine-guanine-guanine (CGG) repeat expansions with over 200 repeats in the fragile X mental retardation 1 (FMR1) gene. Children with FXS are most accessible in special education institutions in Sri Lanka, with a total of approximately 6000 registered attendees. Objectives: The aim of the current study was to estimate the prevalence of FXS among special school attendees and to screen first degree relatives of affected children. Methods: A nationally representative sample of 850 children (5-18 years) was selected using multi-level stratified sampling. Screening was performed by 3' direct triplet primed PCR, followed by melting curve analysis. Expanded repeat status of the screened positives were confirmed using capillary electrophoresis, methylation specific PCR and Southern hybridization. Screening of available first degree relatives (n=12) were carried out using the same method of screening and diagnosis. Results: Eleven had FXS. Prevalence of FXS was 1.3% (95% CI 0.9-1.6). Among the 11 with FXS 9 had more than 350 CGG repeats, while the rest had around 300. Twelve first degree relatives consisting of nine mothers, two female siblings and a male sibling were tested. All mothers and female siblings had either full mutation or premutation while the male sibling had CGG repeats in the normal range. Conclusions: Among the special school attendees, prevalence of FXS was 1.3% which has a high risk for autism and attention deficit hyperactivity disorder.
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The study of circadian rhythms is emerging as a fruitful opportunity for understanding cellular mechanisms that govern human physiology and behavior, fueled by evidence directly linking sleep disorders to genetic mutations affecting circadian molecular pathways. Familial advanced sleep-phase disorder (FASPD) is the first recognized Mendelian circadian rhythm trait, and affected individuals exhibit exceptionally early sleep-wake onset due to altered post-translational regulation of period homolog 2 (PER2). Behavioral and cellular circadian rhythms are analogously affected because the circadian period length of behavior is reduced in the absence of environmental time cues, and cycle duration of the molecular clock is likewise shortened. In light of these findings, we review the PER2 dynamics in the context of circadian regulation to reveal the mechanism of sleep-schedule modulation. Understanding PER2 regulation and functionality may shed new light on how our genetic composition can influence our sleep-wake behaviors.
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Epigênese Genética , Proteínas Circadianas Period/metabolismo , Transtornos do Sono do Ritmo Circadiano/genética , Animais , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Regulação da Expressão Gênica , Humanos , Mutação , Proteínas Circadianas Period/genética , Fosforilação , Processamento de Proteína Pós-Traducional , Transporte Proteico , Vigília/genéticaRESUMO
Individuals with TRPC6 mutations have variable phenotypes, ranging from healthy carrier to focal segmental glomerulosclerosis (FSGS) leading to renal failure. Here, we describe a family where six members had a novel TRPC6 p.R68W (c.202C>T) mutation, two of whom had renal failure from FSGS, and one had proteinuria. One healthy carrier donated a kidney to her sister. Both donor and recipient had no proteinuria at 20 years posttransplant. Two synonymous NPHS1 polymorphisms, rs2285450 (c.294C>T) and rs437168 (c.2289C>T) segregated with renal failure in this family. These variants had higher allele frequencies in 97 unrelated patients with nephrotic syndrome or FSGS compared to 224 controls. Using patch-clamp experiments in HEK293 and podocytes, we showed that the p.R68W mutation increased TRPC6 current amplitudes, which may be explained by enhanced TRPC6 surface expression. Additionally, while wild-type nephrin suppressed TRPC6 currents, this ability was lost in the presence of NPHS1 c.294C>T polymorphism. When cells were transfected according to combined TRPC6 and NPHS1 genotypes in the family, those representing the donor had lower TRPC6 currents than cells representing the recipient, suggesting that interactions between TRPC6 and NPHS1 variants could possibly account for the variable penetrance of TRPC6 mutations and the absence of recurrence in the graft.
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Glomerulosclerose Segmentar e Focal/etiologia , Transplante de Rim/efeitos adversos , Proteínas de Membrana/genética , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Canais de Cátion TRPC/genética , Adolescente , Adulto , Idoso , Animais , Western Blotting , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Seguimentos , Frequência do Gene , Genótipo , Taxa de Filtração Glomerular , Glomerulosclerose Segmentar e Focal/patologia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Células HEK293 , Humanos , Lactente , Testes de Função Renal , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Linhagem , Fenótipo , Podócitos , Complicações Pós-Operatórias , Prognóstico , Recidiva , Fatores de Risco , Canal de Cátion TRPC6 , Adulto JovemRESUMO
Current methods for studying central nervous system myelination necessitate permissive axonal substrates conducive to myelin wrapping by oligodendrocytes. We have developed a neuron-free culture system in which electron-spun nanofibers of varying sizes substitute for axons as a substrate for oligodendrocyte myelination, thereby allowing manipulation of the biophysical elements of axonal-oligodendroglial interactions. To investigate axonal regulation of myelination, this system effectively uncouples the role of molecular (inductive) cues from that of biophysical properties of the axon. We use this method to uncover the causation and sufficiency of fiber diameter in the initiation of concentric wrapping by rat oligodendrocytes. We also show that oligodendrocyte precursor cells display sensitivity to the biophysical properties of fiber diameter and initiate membrane ensheathment before differentiation. The use of nanofiber scaffolds will enable screening for potential therapeutic agents that promote oligodendrocyte differentiation and myelination and will also provide valuable insight into the processes involved in remyelination.
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Técnicas de Cultura de Células/métodos , Bainha de Mielina/fisiologia , Nanofibras/química , Nanotecnologia/métodos , Oligodendroglia/citologia , Animais , Proliferação de Células , Feminino , Masculino , Microscopia Eletrônica de Varredura , Polilisina/química , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Cancer of unknown primary origin (CUP) is defined by the presence of pathologically identified metastatic disease without clinical or radiological evidence of a primary tumour. Our objective was to identify incident cases of CUP in Ontario, Canada, and determine the influence of histology and sites of metastases on overall survival (OS). MATERIAL AND METHODS: We used the Ontario Cancer Registry (OCR) and the Same-Day Surgery and Discharge Abstract Database (SDS/DAD) to identify patients diagnosed with CUP in Ontario between 1 January 2000, and 31 December 2005. Patient diagnostic information, including histology and survival data, was obtained from the OCR. We cross-validated CUP diagnosis and obtained additional information about metastasis through data linkage with the SDS/DAD database. OS was assessed using Cox regression models adjusting for histology and sites of metastases. RESULTS: We identified 3564 patients diagnosed with CUP. Patients without histologically confirmed disease (n = 1821) had a one-year OS of 10.9%, whereas patients with confirmed histology (n = 1743) had a one-year OS of 15.6%. The most common metastatic sites were in the respiratory or digestive systems (n = 1603), and the most common histology was adenocarcinoma (n = 939). Three-year survival rates were 3.5%, 5.3%, 41.6% and 3.6% among adenocarcinoma, unspecified carcinoma, squamous cell carcinoma and undifferentiated histology, respectively. Three-year survival rates were 40%, 2.4%, 8.0% and 4.6% among patients with metastases localised to lymph nodes, the respiratory or digestive systems, other specified sites, and unspecified sites, respectively. CONCLUSION: CUP patients in Ontario have a poor prognosis. Some subgroups may have better survival rates, such as patients with metastases localised to lymph nodes and patients with squamous cell histology.
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Adenocarcinoma/mortalidade , Carcinoma de Células Escamosas/mortalidade , Neoplasias do Sistema Digestório/mortalidade , Neoplasias Primárias Desconhecidas/mortalidade , Neoplasias do Sistema Respiratório/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/secundário , Neoplasias do Sistema Digestório/secundário , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/patologia , Ontário/epidemiologia , Modelos de Riscos Proporcionais , Sistema de Registros , Neoplasias do Sistema Respiratório/secundário , Taxa de SobrevidaRESUMO
A requisite component of nervous system development is the achievement of cellular recognition and spatial segregation through competition-based refinement mechanisms. Competition for available axon space by myelinating oligodendrocytes ensures that all relevant CNS axons are myelinated properly. To ascertain the nature of this competition, we generated a transgenic mouse with sparsely labeled oligodendrocytes and establish that individual oligodendrocytes occupying similar axon tracts can greatly vary the number and lengths of their myelin internodes. Here we show that intercellular interactions between competing oligodendroglia influence the number and length of myelin internodes, referred to as myelinogenic potential, and identify the amino-terminal region of Nogo-A, expressed by oligodendroglia, as necessary and sufficient to inhibit this process. Exuberant and expansive myelination/remyelination is detected in the absence of Nogo during development and after demyelination, suggesting that spatial segregation and myelin extent is limited by microenvironmental inhibition. We demonstrate a unique physiological role for Nogo-A in the precise myelination of the developing CNS. Maximizing the myelinogenic potential of oligodendrocytes may offer an effective strategy for repair in future therapies for demyelination.
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Sistema Nervoso Central/patologia , Doenças Desmielinizantes/fisiopatologia , Proteínas da Mielina/metabolismo , Bainha de Mielina/fisiologia , Oligodendroglia/fisiologia , Animais , Western Blotting , Sistema Nervoso Central/citologia , Técnicas de Silenciamento de Genes , Técnicas Histológicas , Camundongos , Camundongos Transgênicos , Microscopia Eletrônica , Microesferas , Proteínas da Mielina/genética , Proteínas Nogo , Oligodendroglia/metabolismo , Oligodendroglia/ultraestrutura , Poliestirenos , RNA Interferente Pequeno/genética , UltracentrifugaçãoRESUMO
Cyprinid herpesvirus 3 (CyHV-3) is a highly contagious virus that causes significant morbidity and mortality in common carp Cyprinus carpio L. and considered to be one of the most important pathogens of koi and common carp worldwide. Cyprinid herpesvirus 3 infected consignments imported from East Asian and South-East Asian regions were identified during quarantine period in Singapore, and virus from a 2005 consignment was successfully isolated in koi fin cells. A combination of sequence analyses and duplex PCR were used to characterize 15 CyHV-3 isolates detected in koi consignments between 2005 and 2011. Sequence analyses of the enlarged 9/5, SphI-5 and TK gene regions identified both the Asian 1 (n = 11) and European 4 (n = 4) genotypes. Duplex PCR analysis of two variable marker regions between ORF29 and ORF30 (marker I) as well as ORF133 and its upstream region (marker II) revealed viruses of genotypes J (I++ II+ ), U/I (I-- II- ), an intermediate genotype (I++ II- ) and a novel genotype, I++ II+Δ , which was identified in viruses from seven different consignments. This novel genotype has a 13-bp deletion in marker II, while maintaining the I++ allele of marker I. The I++ II+Δ genotype may have emerged from East Asian and South-East Asian regions in recent years.