Numerous living organisms possess biophotonic nanostructures that provide colouration and other diverse functions for survival. While such structures have been actively studied and replicated in the ...laboratory, it remains unclear whether they can be used for biomedical applications. Here, we show a transparent photonic nanostructure inspired by the longtail glasswing butterfly (Chorinea faunus) and demonstrate its use in intraocular pressure (IOP) sensors in vivo. We exploit the phase separation between two immiscible polymers (poly(methyl methacrylate) and polystyrene) to form nanostructured features on top of a Si
N
substrate. The membrane thus formed shows good angle-independent white-light transmission, strong hydrophilicity and anti-biofouling properties, which prevent adhesion of proteins, bacteria and eukaryotic cells. We then developed a microscale implantable IOP sensor using our photonic membrane as an optomechanical sensing element. Finally, we performed in vivo testing on New Zealand white rabbits, which showed that our device reduces the mean IOP measurement variation compared with conventional rebound tonometry without signs of inflammation.
Temporal summation of pressure pain is technically more challenging than simple pressure pain thresholds. The current study describes the design, manufacture and validation of a simple mechanical ...test apparatus to assess the temporal summation of deep pressure pain. We release design details into the public domain with the intention of providing free access for researchers especially in low income countries. Utility and validity of the probes were assessed by pressure application in three different experimental setups: A. Identifying potential issues which needed to be addressed to ensure a reliable test procedure (189 tests with 24 testers using four different probes). B. Selecting the most reliable target force curve (one tester conducted 20 tests). C. Estimating classic inter and intra-examiner reliability and comparing probe measures to other QST measures (repeated measures study with counterbalancing). We make recommendations on best use of the probes. Pressure pain thresholds assessed using probes were affected by anatomical test site and testing tool, but not by tester, day or session. Temporal summation of pressure pain was significantly greater than that of a single pressure application. We found no correlation between temporal summation using the probes on the Infra-Spinatus muscle and temporal summation using a pneumatic cuff on the lower leg. The probe was a useful tool for assessing pain intensity and temporal summation of pressure pain intensity, but not for pain thresholds. A number of caveats need to be considered when using the probe, including but not limited to audio cues and target ideal wave function.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Investigation of mitochondrial metabolism is gaining increased interest owing to the growing recognition of the role of mitochondria in health and numerous diseases. Studies of isolated mitochondria ...promise novel insights into the metabolism devoid of confounding effects from other cellular organelles such as cytoplasm. This study describes the isolation of mitochondria from mouse skeletal myoblast cells (C2C12) and the investigation of live mitochondrial metabolism in real‐time using isotope tracer‐based NMR spectroscopy. 3‐13C1pyruvate was used as the substrate to monitor the dynamic changes of the downstream metabolites in mitochondria. The results demonstrate an intriguing phenomenon, in which lactate is produced from pyruvate inside the mitochondria and the results were confirmed by treating mitochondria with an inhibitor of mitochondrial pyruvate carrier (UK5099). Lactate is associated with health and numerous diseases including cancer and, to date, it is known to occur only in the cytoplasm. The insight that lactate is also produced inside mitochondria opens avenues for exploring new pathways of lactate metabolism. Further, experiments performed using inhibitors of the mitochondrial respiratory chain, FCCP and rotenone, show that 2‐13C1acetyl coenzyme A, which is produced from 3‐13C1pyruvate and acts as a primary substrate for the tricarboxylic acid cycle in mitochondria, exhibits a remarkable sensitivity to the inhibitors. These results offer a direct approach to visualize mitochondrial respiration through altered levels of the associated metabolites.
The study demonstrates an intriguing phenomenon, in which lactate is produced from pyruvate inside the mitochondria. The results were confirmed by treating mitochondria with an inhibitor of mitochondrial pyruvate carrier. 2‐13C1acetyl coenzyme A, which is produced from 3‐13C1pyruvate and acts as a primary substrate for the tricarboxylic acid cycle in mitochondria, exhibits a remarkable sensitivity to the inhibitors of the mitochondrial respiratory chain. These results offer a direct approach to visualize mitochondrial respiration through altered levels of the associated metabolites.
Plant lignans and their microbial metabolites, e.g., enterolactone (ENL), may affect bile acid (BA) metabolism through interaction with hepatic receptors. We evaluated the effects of a flaxseed ...lignan extract (50 mg/day secoisolariciresinol diglucoside) compared to a placebo for 60 days each on plasma BA concentrations in 46 healthy men and women (20-45 years) using samples from a completed randomized, crossover intervention. Twenty BA species were measured in fasting plasma using LC-MS. ENL was measured in 24-h urines by GC-MS. We tested for (a) effects of the intervention on BA concentrations overall and stratified by ENL excretion; and (b) cross-sectional associations between plasma BA and ENL. We also explored the overlap in bacterial metabolism at the genus level and conducted in vitro anaerobic incubations of stool with lignan substrate to identify genes that are enriched in response to lignan metabolism. There were no intervention effects, overall or stratified by ENL at FDR < 0.05. In the cross-sectional analysis, irrespective of treatment, five secondary BAs were associated with ENL excretion (FDR < 0.05). In vitro analyses showed positive associations between ENL production and bacterial gene expression of the bile acid-inducible gene cluster and hydroxysteroid dehydrogenases. These data suggest overlap in community bacterial metabolism of secondary BA and ENL.
Hepatocellular carcinoma (HCC) is an aggressive liver cancer with limited effective treatment options. In this study, we selected TLR agonists imiquimod (IMQ), gardiquimod (GARD), GS-9620 and DSR ...6434, and a small molecule checkpoint inhibitor, BMS-202, for characterization of drug loading and release from radiopaque embolic beads (DC Bead LUMI) for potential use in image-guided transarterial embolization (TACE) of HCC. The maximum drug loading capacity and amount of drug released over time were determined by high performance liquid chromatography and compared with the commonly used anthracycline, doxorubicin hydrochloride (Dox). Maximum drug loading was 204.54 ± 3.87, 65.28 ± 3.09, 65.95 ± 6.96, 65.97 ± 1.54, and 148.05 ± 2.24 mg of drug per milliliter of DC Bead LUMI for Dox, GARD, DSR 6434, IMQ, and BMS-202, respectively. Fast loading and subsequent rapid release in saline were observed for IMQ, GARD, and DSR 6434. These drugs could also be partially removed from the beads by repeated washing with de-ionized water suggesting weak interaction with the beads. Aggregation of IMQ was observed in water and saline. GS-9620 partially decomposed in the solubilizing solution, so loading and release were not characterized. Compared to TLR agonists, slower loading and release were observed for Dox and BMS-202. Potential factors influencing drug loading into and release from DC Bead LUMI including steric hinderance, hydrophobicity, drug pKa, and the electrostatic nature of the beads are discussed. The maximum loading capacity of BMS-202 and Dox in DC Bead LUMI exceeded the maximum theoretical loading capacity of the beads expected from ionic interaction alone suggesting additional drug-bead or drug-drug interactions may play a role. Slightly more release was observed for BMS-202 at early time points followed by a slower release compared to Dox. Further study of these drug-bead combinations is warranted in search of new tools for locoregional delivery of immune-modulating agents for treatment of HCC via drug-eluting bead chemoembolization.
We asked if sensation-seeking is linked to premorbid personality characteristics in patients with addictive disorders, or the characteristics follow the sensation-seeking activity. We interpreted the ...former as a state associated with normal rates of dopamine synthesis, and the latter as a trait of individuals with abnormally high rates of synthesis. We previously determined dopaminergic receptor density in striatum, and we now tested the hypothesis that an elevated dopaminergic condition with increased extracellular dopamine and receptor density follows increased dopamine synthesis capacity in highly sensation-seeking individuals, as measured by positron emission tomography of 18 men with tracer fluorodopa (FDOPA). We detected a site in left caudate nucleus where the volume of distribution of FDOPA-derived metabolites correlated negatively with FDOPA metabolite turnover, consistent with decreased metabolite breakdown in highly sensation-seeking subjects. High rates of sensation-seeking attenuated the dopamine turnover in association with a low rate of dopamine recycling, low dopamine oxidation, and elevated extracellular dopamine and receptors in caudate nucleus. In contrast, low rates of sensation-seeking were associated with rapid dopamine recycling, rapid dopamine oxidation, low extracellular dopamine, and low receptor density. We conclude that the modulation of dopaminergic neurotransmission associated with sensation-seeking is a state of sensation-seeking, rather than a trait of personality following abnormal regulation of dopaminergic neurotransmission.
Digitally supported self-management tailored to an individual's need, in addition to usual care, may reduce pain-related disability compared to usual care alone, and patients with low back pain (LBP) ...using mobile health (mHealth) solutions express positive experiences. Hence, implementing mHealth solutions designed to support self-management is desirable from a clinical and patient perspective. Easily accessible mHealth solutions that can support the self-management of patients with LBP are available, but interest may be subgroup specific. Understanding the characteristics and preferences of patients with LBP labeled as interested may help to reach relevant LBP patient groups and inform the development and implementation of effective interventions with mHealth for patients with LBP.
This study aims to explore the proportion of patients with LBP labeled as interested in testing an mHealth solution designed to support self-management in addition to usual care and to assess how these patients differ from those who were labeled as not interested.
This exploratory cross-sectional study analyzed demographic and patient-reported outcomes from the SpineData registry, a Danish registry of patients with LBP in an outpatient setting. Between February and December 2019, the SpineData registry was used to assess the preliminary eligibility of patients for a clinical trial (selfBACK). Patients were labeled as interested or uninterested depending on if they responded to an invitation to be tested for eligibility for the trial Outcomes were selected from the International Classification of Functioning core set of LBP using a clinical approach. Associations were assessed in a backward selection process, and the proportion of variance explained was assessed with pseudo-R
statistic.
This study included 843 patients, with 181 (21%) individuals labeled as interested in participating in the selfBACK trial. Notably, the cohort labeled as interested differed from their uninterested counterparts in two key aspects: age (36-65 years: 116/181, 64.1% vs 347/662, 52.4%; P=.003) and smoking status (smokers: 22/181, 12.5% vs 174/662, 26.6%; P<.001). Those aged 36-65 years had higher odds of being labeled as interested compared to individuals aged 18-35 years (odds ratio OR 0.43, 95% CI 0.26-0.71) and those 65 years or older (OR 0.77, 95% CI 0.53-1.15). Nevertheless, age accounted for only a modest proportion of variance (R
=0.014). Smokers demonstrated lower odds of being labeled as interested (OR 0.39, 95% CI 0.24-0.64), with smoking status explaining a similarly small proportion of variance (R
=0.019). Collectively, age and smoking status accounted for 3.3% of the variance.
Our investigation revealed that 181 (21%) individuals with LBP invited to participate in the mHealth solution trial for self-management expressed interest. Generally, the characteristics of those labeled as interested and uninterested were comparable. Of note, patients aged 36-65 years had a higher frequency of being labeled as interested compared to their younger and older counterparts.
The variability in pain drawing styles and analysis methods has raised concerns about the reliability of pain drawings as a screening tool for nonpain symptoms. In this study, a data-driven approach ...to pain drawing analysis has been used to enhance the reliability. The aim was to identify distinct clusters of pain patterns by using latent class analysis (LCA) on 46 predefined anatomical areas of a freehand digital pain drawing. Clusters were described in the clinical domains of activity limitation, pain intensity, and psychological factors. A total of 21,123 individuals were included from 2 subgroups by primary pain complaint (low back pain (LBP) n = 15,465) or midback/neck pain (MBPNP) n = 5658). Five clusters were identified for the LBP subgroup: LBP and radiating pain (19.9%), radiating pain (25.8%), local LBP (24.8%), LBP and whole leg pain (18.7%), and widespread pain (10.8%). Four clusters were identified for the MBPNP subgroup: MBPNP bilateral posterior (19.9%), MBPNP unilateral posterior + anterior (23.6%), MBPNP unilateral posterior (45.4%), and widespread pain (11.1%). The clusters derived by LCA corresponded to common, specific, and recognizable clinical presentations. Statistically significant differences were found between these clusters in every self-reported health domain. Similarly, for both LBP and MBPNP, pain drawings involving more extensive pain areas were associated with higher activity limitation, more intense pain, and more psychological distress. This study presents a versatile data-driven approach for analyzing pain drawings to assist in managing spinal pain.
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