Intervertebral disc disease (IVDD) is a common musculoskeletal disease affecting about 5% of all individuals. It is characterized by lumbar disc herniation, which causes nerve root irritation, either mechanically or via inflammatory mediators, and results in radiating pain, known as sciatica. Numerous studies have been conducted to identify the causes and risk factors for IVDD. Lifting heavy loads, torsional stress, and motor vehicle driving are among the best-identified environmental risk factors. However, it has become evident recently from family and twin studies that genetic factors may also be important in IVDD. This hypothesis was strengthened by the identification of two collagen IX alleles associated with sciatica and lumbar disc herniation. In addition, disc degeneration has been shown to be related to an aggrecan gene polymorphism, a Vitamin D receptor and matrix metalloproteinase-3 gene alleles. This review highlights the genetic role and occupational aspects of IVDD. 相似文献
Background/objectivesTo investigate the association between optical coherence tomography (OCT) markers of lesion activity and changes in visual acuity (VA) during anti-vascular endothelial growth factor (anti-VEGF) therapy of eyes diagnosed with neovascular age-related macular degeneration (nAMD); and how VA and OCT markers are considered in physicians’ decision to retreat with anti-VEGFs.Subjects/methodsRetrospective, non-comparative, non-randomised cohort study involving electronic medical record data collected from 1190 patient eyes with nAMD diagnosis at two sites in the United Kingdom. Two sub-cohorts consisting of 321 and 301 eyes, respectively, were selected for analyses.ResultsIn 321 eyes, absence of IRF or SRF at ≥2 clinic visits resulted in a gain of five ETDRS letters from baseline, compared with two letters gained in eyes with <2 clinic visits with absence of IRF (p = 0.006) or SRF (p = 0.042). Anti-VEGF treatment was administered at 421 clinic visits, and 308 visits were without treatment. Comparing treatment visits with non-treatment visits, the maximum difference in frequency of OCT markers of lesion activity were for intraretinal fluid (IRF; 24% versus 5%) and subretinal fluid (SRF; 32% versus 5%). Pigment epithelial detachment (PED) was reported in 58% of treatment visits compared with 36% in non-treatment visits. VA loss was not a consistent trigger for retreatment as it was present in 63% of injection visits and in 49% of non-injection visits.ConclusionsRetreatment decision making is most strongly influenced by the presence of IRF and SRF and less by the presence of PED or VA loss.Subject terms: Outcomes research, Macular degeneration相似文献
Thermal ablation of liver tumors near large blood vessels is affected by the cooling effect of blood flow, leading to incomplete ablation. Hence, we conducted a comparative investigation of heat sink effect in monopolar (MP) and bipolar (BP) radiofrequency ablation (RFA), and microwave (MW) ablation devices.With a perfused calf liver, the ablative performances (volume, mass, density, dimensions), with and without heat sink, were measured. Heat sink was present when the ablative tip of the probes were 8.0 mm close to a major hepatic vein and absent when >30 mm away. Temperatures (T1 and T2) on either side of the hepatic vein near the tip of the probes, heating probe temperature (T3), outlet perfusate temperature (T4), and ablation time were monitored.With or without heat sink, BP radiofrequency ablated a larger volume and mass, compared with MP RFA or MW ablation, with latter device producing the highest density of tissue ablated. MW ablation produced an ellipsoidal shape while radiofrequency devices produced spheres.Percentage heat sink effect in Bipolar radiofrequency : Mono-polar radiofrequency : Microwave was (Volume) 33:41:22; (mass) 23:56:34; (density) 9.0:26:18; and (relative elipscity) 5.8:12.9:1.3, indicating that BP and MW devices were less affected.Percentage heat sink effect on time (minutes) to reach maximum temperature (W) = 13.28:9.2:29.8; time at maximum temperature (X) is 87:66:16.66; temperature difference (Y) between the thermal probes (T3) and the temperature (T1 + T2)/2 on either side of the hepatic vessel was 100:87:20; and temperature difference between the (T1 + T2)/2 and temperature of outlet circulating solution (T4), Z was 20.33:30.23:37.5.MW and BP radiofrequencies were less affected by heat sink while MP RFA was the most affected. With a single ablation, BP radiofrequency ablated a larger volume and mass regardless of heat sink. 相似文献
MR Fingerprinting (MRF)‐based Arterial‐Spin‐Labeling (ASL) has the potential to measure multiple parameters such as cerebral blood flow (CBF), bolus arrival time (BAT), and tissue T1 in a single scan. However, the previous reports have only demonstrated a proof‐of‐principle of the technique but have not examined the performance of the sequence in the context of key imaging parameters. Furthermore, there has not been a study to directly compare the technique to clinically used perfusion method of dynamic‐susceptibility‐contrast (DSC) MRI. The present report consists of two studies. In the first study (N = 8), we examined the dependence of MRF‐ASL sequence on TR time pattern. Ten different TR patterns with a range of temporal characteristics were examined by both simulations and experiments. The results revealed that there was a significance dependence of the sequence performance on TR pattern (p < 0.001), although there was not a single pattern that provided dramatically improvements. Among the TR patterns tested, a sinusoidal pattern with a period of 125 TRs provided an overall best estimation in terms of spatial consistency. These experimental observations were consistent with those of numerical simulations. In the second study (N = 8), we compared MRF‐ASL results with those of DSC MRI. It was found that MRF‐ASL and DSC MRI provided highly comparable maps of cerebral blood flow (CBF) and bolus‐arrival‐time (BAT), with spatial correlation coefficients of 0.79 and 0.91, respectively. However, in terms of quantitative values, BAT obtained with MRF‐ASL was considerably lower than that from DSC (p < 0.001), presumably because of the differences in tracer characteristics in terms of diffusible versus intravascular tracers. Test–retest assessment of MRF‐ASL MRI revealed that the spatial correlations of parametric maps were 0.997, 0.962, 0.746 and 0.863 for B1+, T1, CBF, and BAT, respectively. MRF‐ASL is a promising technique for assessing multiple perfusion parameters simultaneously without contrast agent. 相似文献
Objectives: Conjugated linoleic acid (CLA) isomers have been shown to possess anti-inflammatory activity in the central nervous system. In this study, we aimed to evaluate whether modulation of the fatty acid profile by the CLA isomers c9,t11 or t10,c12CLA was associated with changes in the expression of pro-inflammatory molecules in human astrocytes.
Methods: Cultured astrocytes were treated for 6 days with 100?µM fatty acids (c9,t11CLA or t10,c12CLA or oleic acid). Following the treatment, the fatty acid profile of the cell and pro-inflammatory molecule expression were assessed.
Results: Only the t10,c12CLA isomer induced a significant decrease in arachidonic acid and increased the ratio of docosahexaenoic acid/eicosapentaenoic acid, which constitutes indirect evidence of peroxisome proliferator-activated receptor alpha activation. Inhibition of tumour necrosis factor-α, interleukin-1β, and RANTES expression was observed in astrocytes treated with c9,t11CLA and t10,c12CLA.
Discussion: Current data demonstrate that CLA isomers, particularly t10,c12, may affect neuroinflammation by reducing the pro-inflammatory molecules in cultured astrocytes, suggesting a potential nutritional role of CLA isomers in modulating the astrocyte inflammatory response. 相似文献
Pancreatic cancer is one of the most malignant cancers with a high mortality rate. Some types of pancreatic cancer cells overexpress epidermal growth factor receptor (EGFR), which is a potential target for anticancer agents. In this study, we examined the effect of epidermal growth factor (EGF)-conjugated liposomes containing curcumin (EGF-LP-Cur) on three different EGFR-expressed human pancreatic cancer cell lines, BxPC-3, Panc-1 and Mia Paca-2. We have demonstrated that it is feasible to prepare liposomal vesicles of EGF-LP-Cur and that it is stable in the liquid vehicle at ambient conditions for three weeks. In addition, the formulation of curcumin had higher cytotoxicity on BxPC-3 than on any other cells. It is also shown that the cellular uptake of curcumin on BxPC-3, which is essential for the cytotoxicity, is associated with EGFR-mediated mechanism of action. In summary, our results have showed that targeting EGFR with EGF-conjugated curcumin liposomes enhanced the antitumor activity of curcumin against human pancreatic cancer cells. 相似文献
Autosomal recessive COX4I1 deficiency has been previously reported in a single individual with a homozygous pathogenic variant in COX4I1, who presented with short stature, poor weight gain, dysmorphic features, and features of Fanconi anemia. COX4I1 encodes subunit 4, isoform 1 of cytochrome c oxidase. Cytochrome c oxidase is a respiratory chain enzyme that plays an important role in mitochondrial electron transport and reduces molecular oxygen to water leading to the formation of ATP. Defective production of cytochrome c oxidase leads to a variable phenotypic spectrum ranging from isolated myopathy to Leigh syndrome. Here, we describe two siblings, born to consanguineous parents, who presented with encephalopathy, developmental regression, hypotonia, pathognomonic brain imaging findings resembling Leigh‐syndrome, and a novel homozygous variant on COX4I1, expanding the known clinical phenotype associated with pathogenic variants in COX4I1. 相似文献