We discuss a possible link between the deformation parameter
Θ
μ
ν
arising in the framework of noncommutative geometry and the parameter
β
of the generalized uncertainty principle (GUP). We compute ...the shift of the Hawking temperature induced by the
Θ
μ
ν
-deformed Schwarzschild geometry, and then we relate it to one obtained by GUP. Results suggest a granular structure of specetime at the Planck scales. The current bounds on
β
allow to constraint the noncommutative parameter
Θ
μ
ν
.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract The potential for RNA-based agents to serve as effective therapeutics for central nerve systems (CNS) disorders has been successfully demonstrated in vitro . However, the blood–brain barrier ...limits the distribution of systemically administered therapeutics to the CNS, posing a major challenge for drug development aimed at combatting CNS disorders. Therefore, the development of effective strategies to enhance siRNA delivery to the brain is of great interest in clinical and pharmaceutical fields. To improve the efficiency of small interfering RNA (siRNA) delivery to the brain, we developed a nose-to-brain delivery system combined with cell-penetrating peptide (CPP) modified nano-micelles comprising polyethylene glycol–polycaprolactone (PEG–PCL) copolymers conjugated with the CPP, Tat (MPEG–PCL–Tat). In this study, we describe intranasal brain delivery of siRNA or dextran (Mw: 10,000 Da) as a model siRNA, by using MPEG–PCL–Tat. Intranasal delivery of dextran with MPEG–PCL–Tat improved brain delivery compared to intravenous delivery of dextran either with or without MPEG–PCL–Tat. We also studied the intranasal transfer of MPEG–PCL–Tat to the brain via the olfactory and trigeminal nerves, the putative pathways to the brain from the nasal cavity. We found that MPEG–PCL–Tat accelerated transport along the olfactory and trigeminal nerve pathway because of its high permeation across the nasal mucosa.
•Circulating miR-19b and miR-25 levels were high in pregnant Japanese Black cows.•Circulating miR-29a and miR-148a levels were high in pregnant Japanese Black cows.•Their levels remained same during ...the estrous cycle.•They could be used as potential biomarkers for early pregnancy diagnosis in cattle.•Circulating miR-2455 is a suitable reference miRNA in Japanese Black cows.
Circulating microRNAs (miRNAs) have been used as biomarkers for various diseases and physiological conditions in humans and mice; studies in domestic animals, particularly cattle, are limited. The importance of early pregnancy diagnosis (especially within the 21-d cow estrous cycle) in the livestock industry is extremely high. This study compared the circulating miRNAs in bred non-pregnant and pregnant Japanese Black cows, explored miRNAs as biomarkers for early pregnancy diagnosis, and established a measurement system that included selecting an appropriate reference miRNA and determining the effect of hemolysis on miRNA quantification in plasma. miRNA was extracted from the plasma of Japanese Black cows on day 21 after artificial insemination and subjected to a customized bovine oligonucleotide microarray for expression analysis. Differentially expressed miRNAs and reference miRNA candidates were selected and validated using reverse transcription-quantitative PCR (RT-qPCR). An appropriate endogenous reference miRNA for normalization was selected using NormFinder software. To evaluate the effect of hemolysis on miRNA quantification, hemolyzed samples were prepared using plasma from four cows in the estrous cycle and subjected to RT-qPCR. A total of 124 miRNAs were detected in bovine plasma by microarray analysis in bred non-pregnant and pregnant cows. The levels of five circulating miRNAs were significantly higher in pregnant cows than in bred non-pregnant cows, and 24 miRNAs were detected only in the pregnant group. NormFinder analysis and RT-qPCR validation showed that miR-2455 was an appropriate reference miRNA in the plasma of bred non-pregnant and pregnant Japanese Black cows, and miR-19b, miR-25, miR-29a, and miR-148a were significantly higher in the pregnant group. These four circulating miRNAs did not change during the estrous cycle and were less affected by hemolysis. In the current study, we found four miRNAs, miR-19b, miR-25, miR-29a, and miR-148a, which were present at high levels in the plasma of pregnant Japanese Black cows. Since these miRNAs are less affected by hemolysis, they may potentially be used as biomarkers for early pregnancy diagnosis in cattle.
Summary
To investigate possible roles of T helper type 2 (Th2) cytokines in the anti‐arthritic effects of a blood fluke, Schistosoma mansoni (Sm), for mouse collagen‐induced arthritis (CIA), ...wild‐type (WT), signal transducer and activator of transcription 6 (STAT6) knock‐out (KO) and interleukin (IL)‐10 KO mice were infected with Sm. Three weeks after infection, the mice were immunized with bovine type II collagen (IIC). Arthritis severity was monitored by scoring, measurement of paw thickness and the presence of ankylosis. Serum anti‐IIC IgG levels, splenic cytokine production and cytokine gene expression in the popliteal lymph nodes (PLNs) were measured and compared among WT and gene‐KO mice. Consistent with our previous findings, Sm infection reduced the arthritis severity in WT mice. Splenic production of IL‐17A and tumor necrosis factor (TNF)‐α was reduced by the infection. In contrast, Sm infection markedly exacerbated CIA in STAT6 KO mice. In the KO mice, IL‐17A production was increased by the infection. Conversely, Sm infection did not affect the exacerbated arthritis in IL‐10 KO mice, although IL‐17A production was reduced by the helminth. Our results suggest that signaling via STAT6 (presumably IL‐4 and/or IL‐13) and IL‐10 is required for the suppression of CIA by Sm infection, but through different mechanisms. STAT6 was essential for helminth‐induced reduction of IL‐17A, whereas regulation of the basal arthritis severity by IL‐10 was needed in order for it to be sufficiently suppressed by the helminth.
Schistosoma mansoni infection reduces severity of collagen‐induced arthritis in mice. STAT6‐ mediated signaling and IL‐10 are essential for the anti‐arthritic effects of the helminth.
To verify the reliability and validity of FLIR ONE, a device connected to a smartphone, for the assessment of inflammation based on relative temperature increase compared with the thermography ...routinely used in pressure ulcer (PU) and diabetic foot assessment.
Participants in this pilot cross-sectional observational study were recruited from the patients in the PU team rounds and the diabetic foot outpatient clinic at the university hospital in January 2015. Cohen's kappa coefficient with its 95% confidence intervals was used to evaluate the criterion-related validity and inter- and intra-rater reliability for the thermal imaging assessment. For assessing criterion-related validity, a hand-held high-end infrared thermography device was used to provide reference data. Comparison of thermal images between the smartphone-connected device and the hand-held device was performed with both a 'predetermined range' and an 'automatically-set range.' For assessing inter-rater reliability, two assessors evaluated the thermal images taken by the mobile thermography. For assessing intra-rater reliability, one assessor evaluated the thermal images twice. The thermal images were shown to the assessors at random.
Among 16 thermal images obtained from eight patients, kappa coefficients for each value were as follows: for the predetermined range and automatically-set range, respectively, the criterion-related validity was 1.00 (95% confidence interval 1.00-1.00) and 1.00 (95% confidence interval 1.00-1.00); the inter-rater reliability was 1.00 (95% confidence interval 1.00-1.00) and 1.00 (95% confidence interval 1.00-1.00); and the intra-rater reliability was 1.00 (95% confidence interval 1.00-1.00) and 1.00 (95% confidence interval 1.00-1.00).
This pilot study suggests that FLIR ONE can work as an alternative device for assessing subclinical inflammation in PUs and the diabetic foot in clinical settings. Our results may facilitate clinicians in accepting the routine use of thermal imaging assessment at the patients' bedside.
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Drug delivery from topically instilled eye drops to the posterior segment of the eye has long been one of the greatest challenges of ocular drug development. We developed methods of ...liposome preparation utilizing a microfluidizer to achieve adjustable nanoparticle size (even less than 80nm) and high loading capacity of plasmid DNA. The microfluidizing process parameters were shown to affect the size of the liposomes. Higher operating pressures and passage for at least 10 times through the microfluidizer produced small liposomes with narrow size distribution. The liposomes were physically stable for several months at +4°C. In vivo distribution of the optimized liposome formulations in the rat eyes was investigated with confocal microscopy of the histological specimens. Transferrin was used as a targeting ligand directed to retinal pigment epithelium. Size dependent distribution of liposomes to different posterior segment tissues was seen. Liposomes with the diameter less than 80nm permeated to the retinal pigment epithelium whereas liposomes with the diameter of 100nm or more were distributed to the choroidal endothelium. Active targeting was shown to be necessary for liposome retention to the target tissue. In conclusion, these microfluidizer produced small liposomes in eye drops are an attractive option for drug delivery to the posterior segment tissues of the eye.
The anodic oxidation behavior of Fe–6Cr during potentio-dynamic polarization in pH 4.5 Na2SO4 solution was investigated by electrochemical ellipso-microscopy. Active, passive, and trans-passive ...states of the Fe–6Cr surface showed heterogeneous oxidation behaviors depending on the substrate micro-structure, electrode potential and solution convection. Enhancement of mass-transport by solution injection in the latter half of the active state resulted in acceleration of passivation of the Fe–6Cr surface. The passivity-current density of the surface passivated by intentional convection was reduced to almost half of the current density of the surface that had been in the passive state in a stagnant solution, and the surface passivated by intentional convection showed better resistance against pitting in a chloride-containing solution. The improvement of passivity of the surface was attributed to the formation of a Cr-enriched passive film by a decrease in the thickness of the diffusion layer in the latter half of the active state.
In a previous study, we demonstrated that inflammation suppressed inward rectifying K(+) (Kir) currents in satellite glial cells (SGCs) from the trigeminal ganglia (TRGs) and that this impairment of ...glial potassium homeostasis in the trigeminal ganglion (TRG) contributed to trigeminal pain. The aim of the present study was to investigate whether activation of GABAB receptors modulates the Kir current in SGCs using in vivo patch-clamp and immunohistochemical techniques. Immunohistochemically, we found that immunoreactivity for glial-specific Kir channel subunit Kir4.1 and the GABAB receptor was co-expressed in SGCs from the TRGs. In vivo whole-cell recordings were made using SGCs from the TRGs of urethane-anesthetized rats. Application of baclofen, a GABAB receptor agonist, significantly increased the mean peak amplitude of Kir currents in a concentration-dependent and reversible manner. Baclofen-induced potentiation of the Kir current was abolished by co-application of 3-amino-2-(4-chlorophenyl)-2-hydroxyprophylsulfonic acid (saclofen). In addition, baclofen significantly potentiated the density of the Ba(2+)-sensitive Kir current, and resulted in hyperpolarization of the mean membrane potential. These results suggest that activation of GABAB receptors potentiates the Kir current in SGCs and that GABA released from the TRG neuronal soma could contribute to buffering of extracellular K(+) concentrations following excitation of TRG neurons during the processing of sensory information, including the transmission of noxious stimuli.
Highlights • Immunoreactivity for Kir4.1 and the GABAB receptor was co-expressed in SGCs from the TRGs. • Baclofen-induced potentiation of the Kir current was abolished by co-application of saclofen. ...• Baclofen resulted in hyperpolarization of the membrane potential of SGCs. • Activation of GABAB receptors in SGCs potentiates Kir currents in the absence of inflammation. • GABA contributes to glial potassium homeostasis via SGCs GABAB receptor activation.
Cerebral venous sinus thrombosis is rare and might be overlooked by healthcare providers. It often occurs in the transverse sinuses, superior sagittal sinus, and the vein of Trolard. Sphenoparietal ...sinus (SPS) and/or superficial middle cerebral vein (SMCV) thrombosis is rare and only 12 cases reported in the literature.
We report a 47-year-old woman with iron deficiency anemia associated with myoma uteri who developed left SPS and SMCV thrombosis. She presented with sudden unconsciousness, right hemiplegia, and aphasia. Brain computed tomography showed subcortical hemorrhages in the left frontal and temporal lobes. Magnetic resonance imaging did not reveal the cause of the bleeding. Although antihypertensive treatment with nicardipine was initiated, she deteriorated into coma the next day and underwent emergency decompressive craniectomy. Thrombosis of the SMCV was identified during surgery. Re-examination of preoperative T2 star-weighted imaging revealed thrombosis of the SPS and SMCV.
All but one of the reviewed cases had the thrombosis develop on the left side, which may be attributed to anatomical and brain functional laterality. When an edematous change or cortical hemorrhage of unknown cause is encountered within the perisylvian region, especially on the left side, the possibility of SPS and SMCV thrombosis should be considered.
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