RESUMO
We investigated whether the upper limb muscle stiffness quantified by the acoustic radiation force impulse shear wave elastography (ARFI/SWE) is a potential biomarker for age-related muscle alteration and functional decline in patients with Duchenne muscular dystrophy (DMD). 37 patients with DMD and 30 typically developing controls (TDC) were grouped by age (3-8, 9-11, and 12-18 years). ARFI/SWE measured the biceps and deltoid muscle's shear wave velocities (SWVs). Performance of Upper Limb Module (PUL 1.2 module) assessed muscle function in DMD patients. Mann Whitney test compared muscle SWVs between DMD and TDC, stratified by three age groups. We used analysis of variance with Bonferroni correction to compare muscle SWVs between DMD and TDC and correlated muscle SWVs with PUL results in the DMD group. Results showed that the SWVs of biceps differentiated DMD patients from TDC across age groups. Younger DMD patients (3-8 years) exhibited higher SWVs (p = 0.013), but older DMD patients (12-18 years) showed lower SWVS (p = 0.028) than same-aged TDC. DMD patients had decreasing biceps SWVs with age (p < 0.001), with no such age effect in TDC. The SWVs of deltoid and biceps positively correlated with PUL scores (r = 0.527 â¼ 0.897, P < 0.05) and negatively correlated with PUL timed measures (r = -0.425 â¼ -0.542, P < 0.05) in DMD patients. Our findings suggest that ARFI/SWE quantifying the SWVs in upper limb muscle could be a potential biomarker to differentiate DMD from TDC across ages and that DMD patients showed age-related muscle alteration and limb functional decline.
Assuntos
Técnicas de Imagem por Elasticidade , Distrofia Muscular de Duchenne , Humanos , Distrofia Muscular de Duchenne/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Extremidade Superior , Músculo Esquelético/diagnóstico por imagem , Acústica , BiomarcadoresRESUMO
Ectopic ATP synthase complex (eATP synthase), located on cancer cell surface, has been reported to possess catalytic activity that facilitates the generation of ATP in the extracellular environment to establish a suitable microenvironment and to be a potential target for cancer therapy. However, the mechanism of intracellular ATP synthase complex transport remains unclear. Using a combination of spatial proteomics, interaction proteomics, and transcriptomics analyses, we find ATP synthase complex is first assembled in the mitochondria and subsequently delivered to the cell surface along the microtubule via the interplay of dynamin-related protein 1 (DRP1) and kinesin family member 5B (KIF5B). We further demonstrate that the mitochondrial membrane fuses to the plasma membrane in turn to anchor ATP syntheses on the cell surface using super-resolution imaging and real-time fusion assay in live cells. Our results provide a blueprint of eATP synthase trafficking and contribute to the understanding of the dynamics of tumor progression.
Assuntos
Mitocôndrias , Neoplasias , Humanos , Mitocôndrias/metabolismo , Membrana Celular/metabolismo , Membranas Mitocondriais/metabolismo , Neoplasias/metabolismo , Trifosfato de Adenosina/metabolismo , Microambiente TumoralRESUMO
BACKGROUND: Glucocorticoid-remediable aldosteronism (GRA) is a form of heritable hypertension caused by a chimeric fusion resulting from unequal crossing over between 11ß-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2), which are two genes with similar sequences. Different crossover patterns of the CYP11B1 and CYP11B2 chimeric genes may be associated with a variety of clinical presentations. It is therefore necessary to develop an efficient approach for identifying the differences between the hybrid genes of a patient with GRA. RESULTS: We developed a long-read analysis pipeline named GRAde (GRA deciphering), which utilizes the nonidentical bases in the CYP11B1 and CYP11B2 genomic sequences to identify and visualize the chimeric form. We sequenced the polymerase chain reaction (PCR) products of the CYP11B1/CYP11B2 chimeric gene from 36 patients with GRA using the Nanopore MinION device and analyzed the sequences using GRAde. Crossover events were identified for 30 out of the 36 samples. The crossover sites appeared in the region exhibiting high sequence similarity between CYP11B1 and CYP11B2, and 53.3% of the cases were identified as having a gene conversion in intron 2. More importantly, there were six cases for whom the PCR products indicated a chimeric gene, but the GRAde results revealed no crossover pattern. The crossover regions were further verified by Sanger sequencing analysis. CONCLUSIONS: PCR-based target enrichment followed by long-read sequencing is an efficient and precise approach to dissecting complex genomic regions, such as those involved in GRA mutations, which could be directly applied to clinical diagnosis. The scripts of GRAde are available at https://github.com/hsu-binfo/GRAde .
Assuntos
Citocromo P-450 CYP11B2 , Hiperaldosteronismo , Esteroide 11-beta-Hidroxilase , Citocromo P-450 CYP11B2/genética , Humanos , Hiperaldosteronismo/genética , Proteínas Mutantes Quiméricas , Mutação , Esteroide 11-beta-Hidroxilase/genéticaRESUMO
Duchenne muscular dystrophy (DMD) is a progressive muscular disease, but validated imaging tools to quantify muscle microstructure alteration as mobility declines are lacking. We aimed to determine the feasibility of using acoustic radiation force impulse shear-wave elastography (ARFI/SWE) in the quantitative assessment of lower limb muscle stiffness in DMD patients. Shear wave velocities (SWVs) of lower limbs were measured in 39 DMD patients and 36 healthy controls aged 3-20 y. Mean SWV values of the controls and of the DMD patients at different ambulatory stages were compared using analysis of variance with Bonferroni correction. The DMD group had increased lower limb muscle stiffness compared with controls. Stiffness of the tibialis anterior and medial gastrocnemius muscle decreased from ambulatory to early non-ambulatory stages, whereas stiffness of the rectus femoris muscle increased from ambulatory to late non-ambulatory stages. We describe how SWV changes in lower limb muscles have the potential to predict ambulatory decline in DMD.
Assuntos
Técnicas de Imagem por Elasticidade , Distrofia Muscular de Duchenne , Acústica , Humanos , Extremidade Inferior/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Distrofia Muscular de Duchenne/diagnóstico por imagem , CaminhadaRESUMO
Hepatoma is the second leading cause of cancer death worldwide. Due to the poor outcomes of patients with late diagnosis, newer treatments for hepatoma are still needed. As an emerging therapy, boron neutron capture therapy (BNCT) may be an effective solution in hepatoma management. In this study, boric acid (BA) was used as the boron drug for in vivo analysis of action mechanism. The N1S1 single liver tumor-bearing rat and the VX2 multifocal liver tumor-bearing rabbit models were used to investigate the retention status of BA in the tumor regions during BNCT. The autoradiographic examination showed BA can localize specifically not only in the hepatoma cells but also in tumor blood vessels. Our findings indicate that superior hepatoma targeting could be achieved in BA-mediated BNCT, which supports BA to be a suitable boron drug for BNCT for hepatoma.
Assuntos
Ácidos Bóricos/uso terapêutico , Terapia por Captura de Nêutron de Boro/métodos , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Animais , Ácidos Bóricos/administração & dosagem , Ácidos Bóricos/toxicidade , Carcinoma Hepatocelular/irrigação sanguínea , Humanos , Injeções Intravenosas , Neoplasias Hepáticas/irrigação sanguínea , Masculino , Coelhos , Ratos , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND/AIM: Most patients with hepatocellular carcinoma (HCC) cannot be treated using traditional therapies. Boron neutron capture therapy (BNCT) may provide a new treatment for HCC. In this study, the therapeutic efficacy and radiobiological effects of boric acid (BA)-mediated BNCT in a VX2 multifocal liver tumor-bearing rabbit model are investigated. MATERIALS AND METHODS: Rabbits were irradiated with neutrons at the Tsing Hua Open Pool Reactor 35 min following an intravenous injection of BA (50 mg 10B/kg BW). The tumor size following BNCT treatment was determined by ultrasonography. The radiobiological effects were identified by histopathological examination. RESULTS: A total of 92.85% of the tumors became undetectable in the rabbits after two fractions of BNCT treatment. The tumor cells were selectively eliminated and the tumor vasculature was collapsed and destroyed after two fractions of BA-mediated BNCT, and no injury to the hepatocytes or blood vessels was observed in the adjacent normal liver regions. CONCLUSION: Liver tumors can be cured by BA-mediated BNCT in the rabbit model of a VX2 multifocal liver tumor. BA-mediated BNCT may be a breakthrough therapy for hepatocellular carcinoma.
Assuntos
Ácidos Bóricos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/radioterapia , Animais , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/efeitos da radiação , Terapia por Captura de Nêutron de Boro/métodos , Hepatócitos/efeitos dos fármacos , Hepatócitos/efeitos da radiação , Fígado/efeitos dos fármacos , Fígado/efeitos da radiação , Masculino , CoelhosRESUMO
BACKGROUND: Increasing evidence suggests that post-traumatic stress disorder (PTSD) interferes with the immunological system and is correlated with cardiovascular disease, respiratory disease, and chronic pain conditions. However, the association between PTSD and asthma remains unknown. METHODS: A total of 5518 patients with PTSD and 22,072 age- and sex-matched healthy individuals were enrolled between 2001 and 2009 and followed until the end of 2011. Individuals who developed asthma during the follow-up period were identified. RESULTS: During the follow-up period, the patients with PTSD had an increased risk of asthma (hazard ratio [HR] = 2.27), particularly those belonging to the youngest age group (HR = 4.01). The findings were consistent in subsequent sensitivity analyses after the exclusion of the first year of surveillance or allergic disorders. DISCUSSION: This study showed a significant link between PTSD and asthma after adjusting for demographic data and related comorbidities. The risk of developing asthma in patients with PTSD was consistently higher than that in the controls during the study period. Additional studies are necessary to clarify the underlying mechanisms involved in this association between PTSD and asthma.
Assuntos
Asma/diagnóstico , Asma/epidemiologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Adulto , Asma/psicologia , Comorbidade , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/psicologia , Taiwan/epidemiologia , Adulto JovemRESUMO
INTRODUCTION: Clinical research and studies using animal models have revealed a complex and relatively under-explored interaction between prenatal alcohol exposure (PAE) and alterations in sleep-wake behaviors. OBJECTIVES: To utilize a structured naturalistic observation-based methodology, consisting of descriptive elements, to provide insight into possible links between altered sleep and disruptive daytime presentations in children and adolescents with fetal alcohol spectrum disorder (FASD). To apply a similar structured behavioral observation protocol in a PAE animal model to compare outcomes from the experimental and clinical studies utilizing naturalistic observational methodology. METHODS: Forty pediatric patients with FASD (1.8-17.5 yrs, median age 9.4 yrs) and chronic sleep problems were assessed. In the PAE animal model, male offspring from PAE, Pair-Fed (PF), and ad libitum-fed Control (C) groups (n = 8/group) were assessed in the juvenile/preadolescent (23-25 days of age) and adolescent/pubertal (35-36 days of age) periods. RESULTS: In the clinical setting, we found that 95% of children with FASD showed disruptive or externalizing behaviors, 73% showed internalizing behaviors, 93% had circadian rhythm sleep disorders, all had chronic insomnia, and 85% had restless sleep, often with tossing/turning/kicking movements indicative of non-restorative sleep with hypermotor events. In the daytime, individuals showed excessive daytime sleepiness as well as hyperactive/hyperkinetic behaviors, an urge-to-move, and involuntary movements suggestive of hyperarousability. Alterations in sleep/wake behaviors in the PAE animal model paralleled the clinical data in many aspects, demonstrating greater sleep latencies, less total time asleep, more total time awake and longer awake bouts, more position changes, more time in transition, and longer transition bouts in PAE compared to PF and/or control animals. CONCLUSIONS: Thus, our findings provide support for the power and validity of naturalistic observational paradigms in revealing dysregulated sleep-wake behaviors and their association and/or exacerbating relationship with day and nighttime behavioral problems, such as disruptive behaviors, externalizing and internalizing disorders, and daytime sleepiness.
Assuntos
Modelos Animais de Doenças , Transtornos do Espectro Alcoólico Fetal/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal , Transtornos do Sono-Vigília/fisiopatologia , Animais , Criança , Feminino , Humanos , Masculino , Gravidez , Ratos , Estresse Psicológico/psicologia , Gravação em VídeoAssuntos
Cotos de Amputação , Glucocorticoides/uso terapêutico , Neuroma/tratamento farmacológico , Dor/tratamento farmacológico , Neoplasias do Sistema Nervoso Periférico/tratamento farmacológico , Triancinolona/uso terapêutico , Adulto , Amputados , Humanos , Injeções , Masculino , Neuroma/diagnóstico por imagem , Dor/etiologia , Neoplasias do Sistema Nervoso Periférico/diagnóstico por imagem , Ultrassonografia de IntervençãoRESUMO
INTRODUCTION: Advanced video technology is available for sleep-laboratories. However, low-cost equipment for screening in the home setting has not been identified and tested, nor has a methodology for analysis of video recordings been suggested. METHODS: We investigated different combinations of hardware/software for home-videosomnography (HVS) and established a process for qualitative and quantitative analysis of HVS-recordings. A case vignette (HVS analysis for a 5.5-year-old girl with major insomnia and several co-morbidities) demonstrates how methodological considerations were addressed and how HVS added value to clinical assessment. RESULTS: We suggest an "ideal set of hardware/software" that is reliable, affordable (â¼$500) and portable (=2.8 kg) to conduct non-invasive HVS, which allows time-lapse analyses. The equipment consists of a net-book, a camera with infrared optics, and a video capture device. (1) We present an HVS-analysis protocol consisting of three steps of analysis at varying replay speeds: (a) basic overview and classification at 16× normal speed; (b) second viewing and detailed descriptions at 4-8× normal speed, and (c) viewing, listening, and in-depth descriptions at real-time speed. (2) We also present a custom software program that facilitates video analysis and note-taking (Annotator(©)), and Optical Flow software that automatically quantifies movement for internal quality control of the HVS-recording. The case vignette demonstrates how the HVS-recordings revealed the dimension of insomnia caused by restless legs syndrome, and illustrated the cascade of symptoms, challenging behaviors, and resulting medications. CONCLUSION: The strategy of using HVS, although requiring validation and reliability testing, opens the floor for a new "observational sleep medicine," which has been useful in describing discomfort-related behavioral movement patterns in patients with communication difficulties presenting with challenging/disruptive sleep/wake behaviors.
RESUMO
This study analyzes the characteristics of alumina (Al2O3)/water nanofluid to determine the feasibility of its application in an air-cooled heat exchanger for heat dissipation for PEMFC or electronic chip cooling. The experimental sample was Al2O3/water nanofluid produced by the direct synthesis method at three different concentrations (0.5, 1.0, and 1.5 wt.%). The experiments in this study measured the thermal conductivity and viscosity of nanofluid with weight fractions and sample temperatures (20-60°C), and then used the nanofluid in an actual air-cooled heat exchanger to assess its heat exchange capacity and pressure drop under laminar flow. Experimental results show that the nanofluid has a higher heat exchange capacity than water, and a higher concentration of nanoparticles provides an even better ratio of the heat exchange. The maximum enhanced ratio of heat exchange and pressure drop for all the experimental parameters in this study was about 39% and 5.6%, respectively. In addition to nanoparticle concentration, the temperature and mass flow rates of the working fluid can affect the enhanced ratio of heat exchange and pressure drop of nanofluid. The cross-section aspect ratio of tube in the heat exchanger is another important factor to be taken into consideration.