Analysis of Uncertainties in Inductance of Multi-Layered Printed-Circuit Spiral Coils.

Eddy-current sensors are widely used for precise displacement sensing and non-destructive testing. Application of printed-circuit board (PCB) technology for manufacturing sensor coils may reduce the cost of the sensor and enhance the performance by ensuring consistency. However, these prospects depend on the uniformness of the sensor coil. Inductance measurements of sample coils reveal rather considerable variations. In this paper, we investigate the sources of these variations. Through image analysis of cut-away cross-sections of sensor coils, four factors that contribute to the inductance variations are identified: the distance between layers, the distance between tracings, cross-sectional areas, and misalignment among layers. By using and extending existing method of calculating inductance of spiral coils, the inductance distributions are obtained when these factors are randomly varied. A sensitivity analysis shows that the inductance uncertainty is most affected by the uniformness of the spacings between coil traces and the distances between layers. Improvements in PCB manufacturing process can help to reduce the uncertainty in inductance.

A bispecific soluble receptor fusion protein that targets TNF-α and IL-21 for synergistic therapy in inflammatory arthritis.

This study was aimed at investigating the therapeutic effects of BITRAP, a bispecific fusion protein targeting TNF-α and IL-21, on the development of autoimmune arthritis in humans and mice. To verify the effects of BITRAP in human, peripheral blood mononuclear cells were cultured with BITRAP under IL-17-producing T (Th17) cell-polarizing conditions or osteoclast differentiation conditions. BITRAP treatment inhibited the production of IL-17 and vascular endothelial growth factor but increased the production of IL-10 in CD4+ T cells, as well as directly suppressed osteoclastogenesis. Collagen-induced arthritis (CIA) and IL-1R antagonist (IL-1Ra) knockout mice were treated with BITRAP. Following injection in CIA mice, BITRAP rapidly migrated into the inflamed joints and remained there for 72 hours. Application of BITRAP attenuated the severity of autoimmune arthritis in CIA and IL-1Ra knockout mice by reducing the numbers of inflammatory cytokine-expressing cells and Th17 cells and antibody secretion. Finally, BITRAP suppressed STAT3 phosphorylation, as well as production of IL-17 and TNF-α, in murine splenic CD4+ T cells. These findings suggest that BITRAP, a bispecific fusion protein targeting TNF-α and IL-21, may be an effective treatment to overcome the limitations of anti-TNF therapy for patients with rheumatoid arthritis.

3D Bioprinting for Artificial Pancreas Organ.

Type 1 diabetes mellitus (T1DM) results from an autoimmune destruction of insulin-producing beta cells in the islet of the endocrine pancreas. Although islet transplantation has been regarded as an ideal strategy for T1D, transplanted islets are rejected from host immune system. To immunologically protect them, islet encapsulation technology with biocompatible materials is emerged as an immuno-barrier. However, this technology has been limited for clinical trial such as hypoxia in the central core of islet bead, impurity of islet bead and retrievability from the body. Recently, 3D bioprinting has been emerged as an alternative approach to make the artificial pancreas. It can be used to position live cells in a desired location with real scale of human organ. Furthermore, constructing a vascularization of the artificial pancreas is actualized with 3D bioprinting. Therefore, it is possible to create real pancreas-mimic artificial organ for clinical application. In conclusion, 3D bioprinting can become a new leader in the development of the artificial pancreas to overcome the existed islet.

Comparison of the Efficacy and Safety of Aripiprazole Versus Bupropion Augmentation in Patients With Major Depressive Disorder Unresponsive to Selective Serotonin Reuptake Inhibitors: A Randomized, Prospective, Open-Label Study.

PURPOSE: The purpose of this study was to compare the efficacy and safety of aripiprazole versus bupropion augmentation in patients with major depressive disorder (MDD) unresponsive to selective serotonin reuptake inhibitors (SSRIs). METHODS: This is the first randomized, prospective, open-label, direct comparison study between aripiprazole and bupropion augmentation. Participants had at least moderately severe depressive symptoms after 4 weeks or more of SSRI treatment. A total of 103 patients were randomized to either aripiprazole (n = 56) or bupropion (n = 47) augmentation for 6 weeks. Concomitant use of psychotropic agents was prohibited. Montgomery Asberg Depression Rating Scale, 17-item Hamilton Depression Rating scale, Iowa Fatigue Scale, Drug-Induced Extrapyramidal Symptoms Scale, Psychotropic-Related Sexual Dysfunction Questionnaire scores were obtained at baseline and after 1, 2, 4, and 6 weeks of treatment. RESULTS: Overall, both treatments significantly improved depressive symptoms without causing serious adverse events. There were no significant differences in the Montgomery Asberg Depression Rating Scale, 17-item Hamilton Depression Rating scale, and Iowa Fatigue Scale scores, and response rates. However, significant differences in remission rates between the 2 groups were evident at week 6 (55.4% vs 34.0%, respectively; P = 0.031), favoring aripiprazole over bupropion. There were no significant differences in adverse sexual events, extrapyramidal symptoms, or akathisia between the 2 groups. CONCLUSIONS: The present study suggests that aripiprazole augmentation is at least comparable to bupropion augmentation in combination with SSRI in terms of efficacy and tolerability in patients with MDD. Both aripiprazole and bupropion could help reduce sexual dysfunction and fatigue in patients with MDD. Aripiprazole and bupropion may offer effective and safe augmentation strategies in patients with MDD who are unresponsive to SSRIs. Double-blinded trials are warranted to confirm the present findings.

Fn14-Fc suppresses germinal center formation and pathogenic B cells in a lupus mouse model via inhibition of the TWEAK/Fn14 Pathway.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune-mediated chronic inflammatory disease. Half of patients with SLE suffer from lupus nephritis, which is major cause of death in SLE. TNF-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) interactions mediate inflammatory responses that are linked to the pathogenesis of lupus nephritis. Blocking of the TWEAK/Fn14 pathway by Fn14-Fc was performed in a SLE mouse model and the likely therapeutic mechanisms were investigated. METHODS: To investigate the impact of TWEAK on B cell differentiation in SLE, the levels of AID, Blimp-1, and IRF4 messenger RNA were measured in CD19(+) B cells extracted from the spleens of sanroque mice and cultured with TWEAK. To identify the therapeutic effects of Fn14-Fc in SLE, sanroque mice were treated with Fn14-Fc or a control-Fc for 3 weeks. Immunoglobulin (Ig) G, IgG1, IgG2a, and anti-dsDNA antibody (Ab) levels were measured in the sera of each group. Spleens from each group were stained with antibodies against CD4, B220, GL-7, CD138, and PD-1. Kidneys were stained with hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS). RESULTS: Administration of TWEAK increased the mRNA levels of AID, Blimp-1, and IRF4. Treatment with Fn14-Fc suppressed levels of IgG, IgG1, IgG2a, and anti-dsDNA Ab in sera and reduced numbers of B, plasma, and follicular helper T (Tfh) cells in spleens of sanroque mice. In addition, renal protective effects of Fn14-Fc were shown. CONCLUSION: Fn14-Fc had beneficial effects in a SLE mouse model by repressing B cells, plasma cells, Tfh, and renal damage. This suggested that Fn14-Fc represents a potential therapeutic agent for SLE.

A Retrospective study on the association between vitreous degeneration and cataract in dogs.

OBJECTIVE: This study was performed to evaluate the relationship between cataract and vitreous degeneration on ultrasonography (VDU) in dogs. MATERIALS AND METHODS: Medical records of dogs were retrospectively reviewed. The dogs presented at the Veterinary Medical Teaching Hospital of Seoul National University from January 2009 to December 2011 for ocular ultrasonography to investigate the suitability of the patient for cataract surgery. A total of 97 dogs (179 eyes) were included in this study. Data collected included age, gender, ophthalmic examination, and ultrasonographic examination. Cataract was classified into five grades by ophthalmic examination (0: normal, 1: incipient, 2: immature, 3: mature, and 4: hypermature). VDU was classified into 4 grades (0: no degeneration, 1: mild vitreous degeneration, 2: moderate vitreous degeneration, and 3: marked vitreous degeneration). RESULTS: The mean rank of VDU grades increased with the progression of cataracts, and statistical significant differences were shown between cataracts grade 0 and 2 (P = 0.010), between 0 and 3 (P < 0.001), between 0 and 4 (P = 0.010), between 1 and 3 (P = 0.03), between 1 and 4 (P = 0.02), and between 2 and 4 (P = 0.04). There were no significant differences in age and gender according to the cataract grades. There was no statistical significant difference in the mean rank of VDU grades between cataractous eyes with lens-induced uveitis (LIU) and those without LIU. CONCLUSIONS: The results indicated that increased VDU was associated with more severe cataract grades in dogs.

Corneal plaque containing levofloxacin in a dog.

A 13-year-old castrated male Yorkshire terrier developed a corneal ulcer 2 weeks after intracapsular lens extraction (ICLE) in the right eye. The corneal ulcer was treated with levofloxacin eye drops. A plaque with a white luster developed in the central cornea 2 weeks after treatment with levofloxacin eye drops. The corneal plaque was surgically removed under inhalant anesthesia. The corneal plaque displayed antimicrobial activity against Escherichia coli. Furthermore, levofloxacin content in the plaque was confirmed by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry (MS). The corneal ulcer completely resolved 2 weeks after the surgical removal of the corneal lesion and replacement of levofloxacin eye drops with tobramycin eye drops. Although the topical use of levofloxacin is unlikely to lead to corneal chemical deposits due to the high water solubility of the drug compared to other topical fluoroquinolones, this patient developed corneal plaque of the antibiotic drop.

TWEAK promotes osteoclastogenesis in rheumatoid arthritis.

Bone destruction is critical in the functional disability of patients with rheumatoid arthritis (RA). Osteoclasts, specialized bone-resorbing cells regulated by cytokines, such as receptor activator of NF-κB ligand (RANKL), are primarily implicated in bone destruction in RA. The aim of the study was to examine whether tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor superfamily, has osteoclastogenic activity in patients with RA and in animal models, including mice with collagen-induced arthritis (CIA) and IL-1 receptor antagonist knockout (IL-1RaKO) mice. TWEAK was increased in the synovium, synovial fluid, and serum of patients with RA and in the synovium of CIA mice and IL-1RaKO mice. TWEAK induced RANKL expression in mixed joint cells and splenocytes from CIA mice, IL-1RaKO mice, and fibroblast-like synoviocytes from patients with RA. Both osteoclast precursor cells and osteoclasts express TWEAK receptor fibroblast growth factor-inducible 14. In addition, TWEAK enhanced in vitro osteoclastogenesis without the presence of RANKL-providing cells and by inducing RANKL expression in fibroblast-like synoviocytes. Moreover, treatment with fibroblast growth factor-inducible 14-Fc inhibited RANKL-induced osteoclastogenesis, indicating that endogenous TWEAK also has osteoclastogenic activity. Our data demonstrated that TWEAK promotes osteoclastogenesis in RA, suggesting that therapeutic strategies targeting TWEAK could be effective for treatment of patients with RA, especially in preventing bone destruction.

The signal compensation method for the neutron flux in the measurement system using self-powered neutron detector.

Self-powered neutron detectors (SPNDs) have been utilized within in-core instrumentation to measure neutron flux for control and core flux mapping in nuclear reactors. To estimate neutron flux with SPNDs, a mathematical dynamic model correlating neutron flux and SPND material has been established. Estimation and signal compensation for neutron flux have primarily been developed using transfer-function-based methods or state-space-based methods. Particularly for the rhodium SPND, to compensate for its delayed response to incident neutron flux input, both groups of compensation methods have been widely applied. This Review details the signal compensation methods of neutron flux using transfer-function-based methods, such as those employing analog circuits, dynamic modeling of neutron flux, compensation of neutron flux, and direct inversion. In addition, signal compensation and estimation of neutron flux using state-space-based methods, such as the Kalman filter and H-infinity filter, are reviewed, along with basic calculations based on certain assumptions. Since there are differences in the characteristics of the two groups of methods for the same type of SPND, review comments are also included regarding the stability of compensation methods, based on results obtained from calculations using certain assumptions.

Comparison of systemic atracurium, retrobulbar lidocaine, and sub-Tenon's lidocaine injections in akinesia and mydriasis in dogs.

OBJECTIVE: To compare the effect of sub-Tenon's lidocaine injections (ST) on akinesia and mydriasis to those of systemic atracurium (AT) and retrobulbar lidocaine injections in dogs. ANIMAL STUDIED: Ten healthy beagle dogs without apparent ocular disease. PROCEDURES: Three treatments were performed on 10 beagle dogs with a minimum 7-day washout period: intravenous injection of AT (0.2 mg/kg, AT group); retrobulbar (RB) injection of 2% lidocaine (2.0 mL, RB group) in one eye; and sub-Tenon's injection of 2% lidocaine (2.0 mL, ST group) in the opposite eye. When the akinesia was not obtained within 10 min, an additional 1 mL of lidocaine was administered in the RB and the ST groups. RESULTS: Onset of akinesia in the AT (1.5 ± 0.9 min) and the ST (3.8 ± 5.8 min) groups was significantly shorter than that in the RB group (9.0 ± 6.5 min). Duration of akinesia in the ST group (116.2 ± 32.8 min) was longer compared to the AT (60.6 ± 23.6 min) and the RB (89.0 ± 52.8 min) groups, even though there was only a significant difference between the AT and the ST groups. Mydriasis was achieved in five eyes in the RB group and nine eyes in the ST group. There was no significant difference in onset (3.6 ± 3.1 and 2.9 ± 2.3 min, respectively) or duration (91.4 ± 31.9 and 102.1 ± 35.8 min, respectively) of mydriasis between the groups. CONCLUSIONS: Sub-Tenon's lidocaine injections provide excellent akinesia and mydriasis compared to systemic AT and retrobulbar lidocaine injections. Therefore, sub-Tenon's anesthesia could be an alternative to the systemic administration of neuromuscular blockers and retrobulbar anesthesia for ophthalmic surgery in dogs.

Towards Visualization Thumbnail Designs That Entice Reading Data-Driven Articles.

As online news increasingly include data journalism, there is a corresponding increase in the incorporation of visualization in article thumbnail images. However, little research exists on the design rationale for visualization thumbnails, such as resizing, cropping, simplifying, and embellishing charts that appear within the body of the associated article. Therefore, in this paper we aim to understand these design choices and determine what makes a visualization thumbnail inviting and interpretable. To this end, we first survey visualization thumbnails collected online and discuss visualization thumbnail practices with data journalists and news graphics designers. Based on the survey and discussion results, we then define a design space for visualization thumbnails and conduct a user study with four types of visualization thumbnails derived from the design space. The study results indicate that different chart components play different roles in attracting reader attention and enhancing reader understandability of the visualization thumbnails. We also find various thumbnail design strategies for effectively combining the charts' components, such as a data summary with highlights and data labels, and a visual legend with text labels and Human Recognizable Objects (HROs), into thumbnails. Ultimately, we distill our findings into design implications that allow effective visualization thumbnail designs for data-rich news articles. Our work can thus be seen as a first step toward providing structured guidance on how to design compelling thumbnails for data stories.

TWEAK promotes the production of Interleukin-17 in rheumatoid arthritis.

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is an inflammatory cytokine that modulates several biological responses by inducing chemokines and proinflammatory cytokines. We hypothesized that TWEAK could promote secretion of IL-17, an amplifier of inflammatory arthritis. To test this, we investigated the capacity of TWEAK to induce IL-17 production in T cells via the fibroblast growth factor-inducible gene 14 (Fn14, also known as TWEAK receptor) signal pathway in rheumatoid arthritis (RA). Fn14 and IL-17 were highly expressed in arthritic tissues of collagen-induced arthritis (CIA) mice. TWEAK induced production of IL-17 alone and synergistically with lipopolysaccharide. In naïve murine T cells, TWEAK promoted Th17 differentiation. The expression of Fn14 was predominant in Th17 cells. TWEAK and IL-17 concentrations were significantly higher in synovial fluid and serum in RA patients than OA patients. In addition, we identified CD4(+)IL-17(+)Fn14(+) cells in synovium from RA patients. TWEAK promoted IL-17 production synergistically with IL-23 or IL-21 and blockade of Fn14 with Fn14-Fc suppressed Th17 differentiation. Conversely, this treatment enhanced Treg differentiation. These results suggest that TWEAK induces IL-17 production and may be a therapeutic target in the treatment of RA.

Accuracy of intraocular pressure measurements in dogs using two different tonometers and plano therapeutic soft contact lenses.

OBJECTIVE: To compare and evaluate the accuracy of intraocular pressure (IOP) measured through a therapeutic contact lens, using applanation (TonoPen XL(®)) and rebound (TonoVet(®)) tonometers in enucleated dog eyes. ANIMALS STUDIED: A total of 30 enucleated eyes from 15 beagle dogs. PROCEDURES: To measure accurate IOP, the anterior chamber of each enucleated eye was cannulated with two 26-gauge needles and two polyethylene tubes were connected vertically to an adjustable reservoir bag of normal saline and a pressure transducer. IOP was measured by the TonoPen XL(®) followed by the TonoVet(®) without a contact lens. After a contact lens was applied to the cornea, IOP was re-measured in the same order. Three consecutive IOP measurements were performed using both tonometers. RESULTS: Without the contact lens, the IOP values obtained by both tonometers correlated well according to the regression analysis (TonoVet(®): γ(2) = 0.98, TonoPen XL(®): γ(2) = 0.97, P < 0.001). The TonoPen XL(®) consistently underestimated values as transducer IOP increased; however, IOP values measured with the TonoPen XL(®) were in close agreement and were less variable than those determined with the TonoVet(®) when a contact lens was applied to the cornea. Bland-Altman analysis was used to determine the lower and upper limits of agreement (TonoVet(®): -29.7 and +21.1 mmHg, TonoPen XL(®): -3.9 and +3.6 mmHg) between the two devices. CONCLUSIONS: This study suggests that the TonoPen XL(®) is a useful tonometer for dogs wearing therapeutic contact lenses, and importantly, contact lenses would not need to be removed prior to IOP measurement.

Effect of oral antioxidants on the progression of canine senile cataracts: a retrospective study.

BACKGROUND: Cataracts are the leading cause of impaired vision or blindness in dogs. There are many antioxidants that can prevent cataract progression, but whether they are clinically effective in dogs has not been established. OBJECTIVES: To analyze the delaying or preventing effect of oral antioxidants on canine senile cataracts through retrospective analysis. METHODS: Medical records of dogs from January 1, 2015 to July 10, 2020 were reviewed. Dogs that were 8 yr of age or older with senile cataracts were included in this study. The dogs were divided into two treatment groups (dogs administered with Ocu-GLO supplement and dogs administered with Meni-One Eye R/C supplement) and a control group (dogs that were not administered any supplement). Dogs with incipient and immature cataracts were included in this study. Altogether, 112 dogs (156 eyes) with incipient cataracts and 60 dogs (77 eyes) with immature cataracts were included. The period of time that cataracts progressed from incipient to immature, and from immature to mature was recorded for each dog. RESULTS: There was no significant delaying effect on the progression of incipient cataracts. However, both Ocu-GLO (hazard ratio = 0.265, p = 0.026) and Meni-One (hazard ratio = 0.246, p = 0.005) significantly delayed the progression of immature cataracts compared to the control group. CONCLUSIONS: Although there was no significant delaying effect of oral antioxidants on incipient cataract progression, antioxidants could be used to delay the progression of senile immature cataract.

TMPRSS2 and TMPRSS4 facilitate trypsin-independent spread of influenza virus in Caco-2 cells.

Proteolysis of influenza virus hemagglutinin by host cell proteases is essential for viral infectivity, but the proteases responsible are not well defined. Recently, we showed that engineered expression of the type II transmembrane serine proteases (TTSPs) TMPRSS2 and TMPRSS4 allows hemagglutinin (HA) cleavage. Here we analyzed whether TMPRSS2 and TMPRSS4 are expressed in influenza virus target cells and support viral spread in the absence of exogenously added protease (trypsin). We found that transient expression of TMPRSS2 and TMPRSS4 resulted in HA cleavage and trypsin-independent viral spread. Endogenous expression of TMPRSS2 and TMPRSS4 in cell lines correlated with the ability to support the spread of influenza virus in the absence of trypsin, indicating that these proteases might activate influenza virus in naturally permissive cells. Indeed, RNA interference (RNAi)-mediated knockdown of both TMPRSS2 and TMPRSS4 in Caco-2 cells, which released fully infectious virus without trypsin treatment, markedly reduced the spread of influenza virus, demonstrating that these proteases were responsible for efficient proteolytic activation of HA in this cell line. Finally, TMPRSS2 was found to be coexpressed with the major receptor determinant of human influenza viruses, 2,6-linked sialic acids, in human alveolar epithelium, indicating that viral target cells in the human respiratory tract express TMPRSS2. Collectively, our results point toward an important role for TMPRSS2 and possibly TMPRSS4 in influenza virus replication and highlight the former protease as a potential therapeutic target.

Effect of central corneal thickness on intraocular pressure with the rebound tonometer and the applanation tonometer in normal dogs.

OBJECTIVE: To evaluate the effect of central corneal thickness (CCT) on the measurement of intraocular pressure (IOP) with the rebound (TonoVet(®)) and applanation (TonoPen XL(®)) tonometers in beagle dogs. ANIMAL STUDIED: Both eyes of 60 clinically normal dogs were used. PROCEDURES: The IOP was measured by the TonoVet(®), followed by the TonoPen XL(®) in half of the dogs, while the other half was measured in the reverse order. All CCT measurements were performed 10 min after the use of the second tonometer. RESULTS: The mean IOP value measured by the TonoVet(®) (16.9 ± 3.7 mmHg) was significantly higher than the TonoPen XL(®) (11.6 ± 2.7 mmHg; P < 0.001). The IOP values obtained by both tonometers were correlated in the regression analysis (γ(2) = 0.4393, P < 0.001). Bland-Altman analysis showed that the lower and upper limits of agreement between the two devices were -0.1 and +10.8 mmHg, respectively. The mean CCT was 549.7 ± 51.0 µm. There was a correlation between the IOP values obtained by the two tonometers and CCT readings in the regression analysis (TonoVet(®) : P = 0.002, TonoPen XL(®) : P = 0.035). The regression equation demonstrated that for every 100 µm increase in CCT, there was an elevation of 1 and 2 mmHg in IOP measured by the TonoPen XL(®) and TonoVet(®), respectively. CONCLUSIONS: The IOP obtained by the TonoVet(®) and TonoPen XL(®) would be affected by variations in the CCT. Therefore, the CCT should be considered when interpreting IOP values measured by tonometers in dogs.

Proteolytic activation of the 1918 influenza virus hemagglutinin.

Proteolytic activation of the hemagglutinin (HA) protein is indispensable for influenza virus infectivity, and the tissue expression of the responsible cellular proteases impacts viral tropism and pathogenicity. The HA protein critically contributes to the exceptionally high pathogenicity of the 1918 influenza virus, but the mechanisms underlying cleavage activation of the 1918 HA have not been characterized. The neuraminidase (NA) protein of the 1918 influenza virus allows trypsin-independent growth in canine kidney cells (MDCK). However, it is at present unknown if the 1918 NA, like the NA of the closely related strain A/WSN/33, facilitates HA cleavage activation by recruiting the proprotease plasminogen. Moreover, it is not known which pulmonary proteases activate the 1918 HA. We provide evidence that NA-dependent, trypsin-independent cleavage activation of the 1918 HA is cell line dependent and most likely plasminogen independent since the 1918 NA failed to recruit plasminogen and neither exogenous plasminogen nor the presence of the A/WSN/33 NA promoted efficient cleavage of the 1918 HA. The transmembrane serine protease TMPRSS4 was found to be expressed in lung tissue and was shown to cleave the 1918 HA. Accordingly, coexpression of the 1918 HA with TMPRSS4 or the previously identified HA-processing protease TMPRSS2 allowed trypsin-independent infection by pseudotypes bearing the 1918 HA, indicating that these proteases might support 1918 influenza virus spread in the lung. In summary, we show that the previously reported 1918 NA-dependent spread of the 1918 influenza virus is a cell line-dependent phenomenon and is not due to plasminogen recruitment by the 1918 NA. Moreover, we provide evidence that TMPRSS2 and TMPRSS4 activate the 1918 HA by cleavage and therefore may promote viral spread in lung tissue.

Evaluation of the mydriatic effect of intracameral lidocaine hydrochloride injection in eyes of clinically normal dogs.

OBJECTIVE-To evaluate the mydriatic effect of intracameral injection of preservative-free 1% and 2% lidocaine hydrochloride solutions and determine the onset and duration of mydriasis according to the concentration and volume of lidocaine administered in healthy dogs. ANIMALS-5 healthy adult Beagles weighing 7 to 10 kg, with no apparent ocular disease. PROCEDURES-A double-blind randomized 9-session crossover trial was designed. Both eyes were assigned to 9 treatments with a minimum 7-day washout period between treatments: 0.1, 0.2, and 0.3 mL of 2% lidocaine solution; 0.1, 0.2, and 0.3 mL of 1% lidocaine solution; and 0.1, 0.2, and 0.3 mL of balanced salt solution. Dogs were anesthetized, and the allocated treatment was injected intracamerally after aspiration of the same volume of aqueous humor from the anterior chamber of each eye. Two perpendicular pupil diameters were measured. Intraocular pressure, heart rate, respiratory rate, ECG readings, and end-tidal partial pressure of CO(2) were monitored. RESULTS-Intracameral injection of 1% or 2% lidocaine solutions in volumes of 0.1 to 0.3 mL induced a significant degree of mydriasis, and the effect was maintained for 74 to 142 minutes. Lidocaine injection had no significant effect on intraocular pressure, heart rate, respiratory rate, ECG readings, or end-tidal partial pressure of CO(2). CONCLUSIONS AND CLINICAL RELEVANCE-Intracameral lidocaine injection in healthy dogs induced mydriasis, the timing of which was affected by concentration and volume of lidocaine. This technique could serve as an alternative to topically administered mydriatics for intraocular surgery in dogs.

Hydrogels with an embossed surface: An all-in-one platform for mass production and culture of human adipose-derived stem cell spheroids.

Stem cell spheroids have been studied extensively in organoid culture and therapeutic transplantation. Herein, hydrogels with an embossed surface (HES) were developed as an all-in-one platform that can enable the rapid formation and culture of a large quantity of size-controllable stem cell spheroids. The embossed structure on the hydrogel was adjustable according to the grit designation of the sandpaper. Human adipose-derived stem cells (hADSCs) were rapidly assembled into spheroids on the hydrogel, with their size distribution precisely controlled from 95 ±â€¯6 µm to 181 ±â€¯15 µm depending on surface roughness. The hADSC spheroids prepared from the HES demonstrated expression of stemness markers and differentiation capacity. In addition, HES-based spheroids showed significantly greater VEGF secretion than spheroids grown on a commercially available low-attachment culture plate. Exploiting those advantages, the HES-based spheroids were used for 3D bioprinting, and the spheroids within the 3D-printed construct showed improved retention and VEGF secretion compared to the same 3D structure containing single cell suspension. Collectively, HES would offer a useful platform for mass fabrication and culture of stem cell spheroids with controlled sizes for a variety of biomedical applications.

Activation of PKCbeta(II) and PKCtheta is essential for LDL-induced cell proliferation of human aortic smooth muscle cells via Gi-mediated Erk1/2 activation and Egr-1 upregulation.

Native LDL may be a mitogenic stimulus of VSMC proliferation in lesions where endothelial disruption occurs. Recent studies have demonstrated that the mitogenic effects of LDL are accompanied by Erk1/2 activation via an unknown G-protein-coupled receptor (GPCR). In this article, we report that LDL translocated PKCbeta(II) and PKCtheta from cytosol to plasma membrane, and inhibition of PKCbeta(II) and PKCtheta decreased LDL effects via the deactivation of Erk1/2. Moreover, pertussis toxin, but not cholera toxin or heparin, inhibited LDL-induced translocation of PKCbeta(II) and PKCtheta, suggesting that Gi protein plays a role in LDL effects. Of LPA, S1P, and LDL, whose signaling is conveyed via Gi/o proteins, only LDL induced translocation of PKCbeta(II) and PKCtheta. Inhibition of PKCbeta(II) or PKCtheta, as well as of Erk1/2 and GPCR, decreases LDL-induced upregulation of Egr-1, which is critical for cell proliferation. This is the first report, to our knowledge, that the participation of PKCtheta in VSMC proliferation is unique.