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ImportanceCOVID-19 vaccination is recommended during pregnancy for the protection of the mother. Little is known about the immune response to booster vaccinations during pregnancy. ObjectiveTo measure immune responses to COVID-19 primary and booster mRNA vaccination during pregnancy and transplacental antibody transfer to the newborn. DesignProspective cohort study of pregnant participants enrolled from July 2021 to January 2022, with follow up through and up to 12 months after delivery. SettingMulticenter study conducted at 9 academic sites. ParticipantsPregnant participants who received COVID-19 vaccination during pregnancy and their newborns. Exposure(s)Primary or booster COVID-19 mRNA vaccination during pregnancy. Main Outcome(s) and Measure(s)SARS-CoV-2 binding and neutralizing antibody (nAb) titers after primary or booster COVID-19 mRNA vaccination during pregnancy and antibody transfer to the newborn. Immune responses were compared between primary and booster vaccine recipients in maternal sera at delivery and in cord blood, after adjusting for days since last vaccination. ResultsIn this interim analysis, 167 participants received a primary 2-dose series and 73 received a booster dose of mRNA vaccine during pregnancy. Booster vaccination resulted in significantly higher binding and nAb titers, including to the Omicron BA.1 variant, in maternal serum at delivery and cord blood compared to a primary 2-dose series (range 0.55 to 0.88 log10 higher, p<0.0001 for all comparisons). Although levels were significantly lower than to the prototypical D614G variant, nAb to Omicron were present at delivery in 9% (GMT ID50 12.7) of Pfizer and 22% (GMT ID50 14.7) of Moderna recipients, and in 73% (GMT ID50 60.2) of boosted participants (p<0.0001). Transplacental antibody transfer was efficient regardless of vaccination regimen (median transfer ratio range: 1.55-1.77 for binding IgG and 1.00-1.78 for nAb). Conclusions and RelevanceCOVID-19 mRNA vaccination during pregnancy elicited robust immune responses in mothers and efficient transplacental antibody transfer to the newborn. A booster dose during pregnancy significantly increased maternal and cord blood antibody levels, including against Omicron. Findings support continued use of COVID-19 vaccines during pregnancy, including booster doses. Trial Registrationclinical trials.gov; Registration Number: NCT05031468; https://clinicaltrials.gov/ct2/show/NCT05031468 Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the immune response after COVID-19 booster vaccination during pregnancy and how does receipt of a booster dose impact transplacental antibody transfer to the newborn? FindingsReceipt of COVID-19 mRNA vaccines during pregnancy elicited robust binding and neutralizing antibody responses in the mother and in the newborn. Booster vaccination during pregnancy elicited significantly higher antibody levels in mothers at delivery and cord blood than 2-dose vaccination, including against the Omicron BA.1 variant. MeaningCOVID-19 vaccines, especially booster doses, should continue to be strongly recommended during pregnancy.
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Purpose@#To investigate the changes in intraocular cytokines after ranibizumab treatment in patients with polypoidal choroidal vasculopathy (PCV). @*Methods@#This multicenter, prospective study enrolled patients with PCV treated with three monthly ranibizumab followed by a pro re nata regimen for 24 weeks. Best corrected visual acuity, slit lamp examination, fundus photography, and optical coherence tomography were performed every 4 weeks. Aqueous humor was collected to measure intraocular cytokines at baseline, week 8, and the time of recurrence or week 20. The association of changes in intraocular cytokines with visual acuity, central macular thickness, central choroidal thickness, area of abnormal vessels, and polyp closure was assessed. @*Results@#This study included 25 eyes. The mean patient age was 70.3 ± 6.1 years. The vascular endothelial growth factor (VEGF) concentration decreased at week 8, but only interferon (IFN)-γ, tissue inhibitors of matrix metalloproteinases (TIMP)-2, and monocyte chemoattractant protein (MCP)-2 decreased at the time of recurrence. The recurrence interval was positively associated with the baseline epithelial-neutrophil activating peptide (ENA)-78, interleukin (IL)-17, leptin, and transforming growth factor-β1, and baseline central macular thickness was positively correlated with the baseline fibroblast growth factor-4 and IL-10. Thick central choroidal thickness was associated with a low basic fibroblast growth factor and high IFN-γ at baseline. The MCP-3 and Tie-2 levels decreased in two eyes with polyp closure. @*Conclusions@#Ranibizumab significantly reduced intraocular VEGF concentrations and consequently improved PCV. However, the cytokines IFN-γ, TIMP-2, and MCP-2, rather than VEGF, were associated with PCV recurrence. Further studies of intraocular cytokines involved in neovascularization in PCV are needed.
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Purpose@#We report bilateral, diffuse, uveal melanocytic proliferation caused by a stomach adenocarcinoma.Case summary: A 78-year-old male complained of visual impairment 3 months in duration. He had diabetes and had undergone cataract surgery on both eyes 4 years prior. His best-corrected visual acuity was counting fingers in the right eye and 20/160 in the left eye. Both intraocular pressures were normal. The anterior segments yielded no specific findings. The maculae exhibited multiple, round, patchy, pigmented or depigmented lesions with exudative retinal detachment. Fluorescein angiography revealed multiple hyperfluorescent lesions. Optical coherence tomography revealed that the hyper-reflective exudates lay between the neurosensory retina and the retinal pigment epithelium. We diagnosed bilateral, diffuse, uveal melanocytic proliferation and performed a systemic evaluation. Computed tomography revealed several mass lesions in the lung, stomach, and lymph nodes; these appeared to be malignant. An esophagogastroduodenoscopic biopsy confirmed that the lesions were adenocarcinomas. @*Conclusions@#A bilateral, diffuse, uveal melanocytic proliferation induced by a primary malignant tumor exhibited multiple, pigmented subretinal exudates associated with exudative macular retinal detachment. In patients with such findings, it is necessary to evaluate the malignant tumor status of remote organs.
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Purpose@#Here, we report a case of acute noninfectious endophthalmitis after removal of silicone oil (SO) and posterior capsulectomy in a patient with proliferative diabetic retinopathy.Case summary: SO removal and posterior capsulectomy were performed in a 61-year-old man who had undergone vitrectomy with combined cataract surgery, membrane peeling, laser photocoagulation, and SO injection to treat vitreous hemorrhage and tractional retinal detachment three months previously. The patient’s best-corrected visual acuity on the day after surgery was 20/50; it decreased to hand motion at five days after SO removal. Exudative membrane with hypopyon, anterior chamber cell (trace), and mild conjunctival injection were observed. The patient did not complain of ocular pain. Topical steroid was applied following a diagnosis of postoperative noninfectious endophthalmitis. The exudative membrane and hypopyon decreased after three days of treatment and had resolved completely after one month of treatment. The patient’s visual acuity improved to 20/50. @*Conclusions@#Noninfectious endophthalmitis can develop after removal of SO and posterior capsulectomy. Topical steroid treatment is effective in such cases.
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Purpose@#To report a case of Streptococcus infantarius endophthalmitis related to the use of a XEN® Gel Stent.Case summary: A 75-year-old male was referred to our practice with a diagnosis of endophthalmitis 55 days after XEN® Gel Stent implantation. He had primary open-angle glaucoma. Visual acuity was 20/50. Slit-lamp examination revealed conjunctival injection and anterior chamber inflammation with hypopyon. Fundus examination showed inflammatory cells with exudative materials in the vitreous. The aqueous sampling for culture of causative micro-organisms was followed by removal of the XEN® Gel Stent, along with anterior chamber irrigation and intracameral and intravitreal injection of antibiotics. Streptococcus infantarius was isolated after 5 days. Vitrectomy, anterior chamber lavage, and intravitreal injection of antibiotics were additionally performed to control the intraocular inflammation. Sixteen days after vitrectomy, the intraocular inflammation disappeared. The choroidal detachment was resolved 34 days after vitrectomy. Visual improvement was limited to 20/100 at 6 months. @*Conclusions@#XEN® Gel Stent-related bacterial endophthalmitis was successfully treated by implant removal, vitrectomy, and proper intraocular antibiotic treatment.
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Associations between periodontal infection and cardiovascular disease have been documented. Porphyromonas gingivalis is a well-established periodontal pathogen, and tissue factor (TF) is a key initiator of the coagulation cascade. In this context, P. gingivalis has been reported to enhance TF expression in human endothelial cells. The present study investigated the underlying mechanisms of TF induction by P. gingivalis in human umbilical vein endothelial cells. P. gingivalis increased TF expression in a dose- and time-dependent manner. Not only live bacteria but also glutaraldehyde-fixed bacteria increased TF expression to the same extent. However, sonicates of P. gingivalis did not induce TF expression. Cytochalasin D and SMIFH2, which are inhibitors of actin polymerization and actin nucleation, respectively, inhibited the TF expression induced by P. gingivalis. Finally, TF production was decreased or increased in the presence of various signaling inhibitors, including mitogen-activated protein kinases. These results suggest that P. gingivalis induces endothelial TF expression by a bacterial internalization-dependent mechanism and through diverse signal transduction mechanisms.
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Purpose@#We report a case of infectious scleritis featuring kissing choroidal detachment and serous retinal detachment.Case summary: A 65-year-old female presented with ocular pain and hyperemia of the right eye 1 week in duration. Anterior chamber inflammation was evident. After pterygium excision, a thinned sclera and loss of conjunctiva around a necrotic lesion were observed. Necrotizing scleritis with anterior uveitis was diagnosed and topical and systemic steroids commenced. After 1 week, the scleral thickness increased, but conjunctival injection and choroidal detachment were newly noticed. Infectious scleritis was suspected and the pterygium excision site cultured. Although empirical antibiotics (fortified ceftazidime and tobramycin) were prescribed, the choroidal and serous retinal detachments became aggravated. Pseudomonas aeruginosa was identified on scleral culture, and topical piperacillin/tazobactam and systemic cefepime (2 g) commenced. Although the antibiotics were appropriate, the choroidal and serous retinal detachments became further aggravated. Necrotic tissue was subjected to surgical debridement. Two days later, the infectious signs had diminished and a systemic steroid was added. Over the next few weeks, all of the choroidal and serous retinal detachments, and the infectious signs, improved. @*Conclusions@#Patients with infectious scleritis featuring severe choroidal detachment and serous retinal detachment resistant to appropriate antibiotics may require surgical debridement of necrotic tissue. After controlling the infectious signs, systemic steroids should be considered to ensure a good prognosis.
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Purpose@#To report the effect of an intravitreal dexamethasone implant on refractory posterior scleritis. @*Methods@#The medical records of patients treated with an intravitreal dexamethasone implant for non-infectious refractory posterior scleritis were retrospectively reviewed, including age, sex, duration of follow-up, and presence of associated systemic diseases. The duration until relapse, changes in visual acuity, number of implants, and side effects associated with the implant were also analyzed. @*Results@#Seven eyes from five patients were included. The mean age was 73.2 ± 12.5 years (59-92 years). Although all patients had been treated with high-dose systemic steroid, and immunosuppressants were added, the posterior scleritis was poorly controlled. The duration from the diagnosis to the first dexamethasone implant was a mean of 8.2 months (3-27 months). The scleritis was well controlled in all eyes until at least 2 months (2-5 months) after inserting the implant. An average of 2.1 (total of 15 times in the seven eyes) implants were inserted. No complications related to the implant were observed other than a temporary increase in intraocular pressure in one eye. @*Conclusions@#Intravitreal dexamethasone implants were an effective treatment option for refractory posterior scleritis.
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Purpose@#To report complications requiring surgical management related to intravitreal dexamethasone implant. @*Methods@#The medical records of patients who received intravitreal dexamethasone implant injection from June 2013 to March 2020 were reviewed retrospectively. Patients who had undergone intraocular surgical management within 6 months after implant injection, with the exception of cataract surgery, were included. Of them, only the cases in which the surgery was definitely related to complications with the Ozurdex implant were included. In these patients, underlying disease, intraocular pressure change, and the number of injections were analyzed. @*Results@#A total of 1,168 injections of 473 eyes (439 patients) were enrolled in the study. The mean number of injections was 2.5 per eye. The mean age was 61.4 ± 11.3 years. The complications requiring an additional surgical procedure occurred in six (0.5%) injections. Of them, four, one, and one eyes showed uveitis, diabetic macular edema, and branch retinal vein occlusion, respectively. Surgical management was performed to control the increased intraocular pressure in two eyes, inappropriate implant location in two eyes, scleral wound leakage in one eye, and retinal detachment in one eye. The incidence of severe complications requiring surgical management was high in cases with a history of previous vitrectomy (p = 0.007, Fisher’s exact test) and uveitis (p = 0.007, Fisher’s exact test). @*Conclusions@#Severe complications requiring surgical management occurred in 0.5% of cases (six cases) after intravitreal dexamethasone implant injections. These complications were related to a history of previous vitrectomy and uveitis. Five eyes recovered to favorable visual function after surgery, with the exception of one eye with retinal detachment.
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Associations between periodontal infection and cardiovascular disease have been documented. Porphyromonas gingivalis is a well-established periodontal pathogen, and tissue factor (TF) is a key initiator of the coagulation cascade. In this context, P. gingivalis has been reported to enhance TF expression in human endothelial cells. The present study investigated the underlying mechanisms of TF induction by P. gingivalis in human umbilical vein endothelial cells. P. gingivalis increased TF expression in a dose- and time-dependent manner. Not only live bacteria but also glutaraldehyde-fixed bacteria increased TF expression to the same extent. However, sonicates of P. gingivalis did not induce TF expression. Cytochalasin D and SMIFH2, which are inhibitors of actin polymerization and actin nucleation, respectively, inhibited the TF expression induced by P. gingivalis. Finally, TF production was decreased or increased in the presence of various signaling inhibitors, including mitogen-activated protein kinases. These results suggest that P. gingivalis induces endothelial TF expression by a bacterial internalization-dependent mechanism and through diverse signal transduction mechanisms.
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Purpose@#We report a case of infectious scleritis featuring kissing choroidal detachment and serous retinal detachment.Case summary: A 65-year-old female presented with ocular pain and hyperemia of the right eye 1 week in duration. Anterior chamber inflammation was evident. After pterygium excision, a thinned sclera and loss of conjunctiva around a necrotic lesion were observed. Necrotizing scleritis with anterior uveitis was diagnosed and topical and systemic steroids commenced. After 1 week, the scleral thickness increased, but conjunctival injection and choroidal detachment were newly noticed. Infectious scleritis was suspected and the pterygium excision site cultured. Although empirical antibiotics (fortified ceftazidime and tobramycin) were prescribed, the choroidal and serous retinal detachments became aggravated. Pseudomonas aeruginosa was identified on scleral culture, and topical piperacillin/tazobactam and systemic cefepime (2 g) commenced. Although the antibiotics were appropriate, the choroidal and serous retinal detachments became further aggravated. Necrotic tissue was subjected to surgical debridement. Two days later, the infectious signs had diminished and a systemic steroid was added. Over the next few weeks, all of the choroidal and serous retinal detachments, and the infectious signs, improved. @*Conclusions@#Patients with infectious scleritis featuring severe choroidal detachment and serous retinal detachment resistant to appropriate antibiotics may require surgical debridement of necrotic tissue. After controlling the infectious signs, systemic steroids should be considered to ensure a good prognosis.
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Purpose@#To report the effect of an intravitreal dexamethasone implant on refractory posterior scleritis. @*Methods@#The medical records of patients treated with an intravitreal dexamethasone implant for non-infectious refractory posterior scleritis were retrospectively reviewed, including age, sex, duration of follow-up, and presence of associated systemic diseases. The duration until relapse, changes in visual acuity, number of implants, and side effects associated with the implant were also analyzed. @*Results@#Seven eyes from five patients were included. The mean age was 73.2 ± 12.5 years (59-92 years). Although all patients had been treated with high-dose systemic steroid, and immunosuppressants were added, the posterior scleritis was poorly controlled. The duration from the diagnosis to the first dexamethasone implant was a mean of 8.2 months (3-27 months). The scleritis was well controlled in all eyes until at least 2 months (2-5 months) after inserting the implant. An average of 2.1 (total of 15 times in the seven eyes) implants were inserted. No complications related to the implant were observed other than a temporary increase in intraocular pressure in one eye. @*Conclusions@#Intravitreal dexamethasone implants were an effective treatment option for refractory posterior scleritis.
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Purpose@#To report complications requiring surgical management related to intravitreal dexamethasone implant. @*Methods@#The medical records of patients who received intravitreal dexamethasone implant injection from June 2013 to March 2020 were reviewed retrospectively. Patients who had undergone intraocular surgical management within 6 months after implant injection, with the exception of cataract surgery, were included. Of them, only the cases in which the surgery was definitely related to complications with the Ozurdex implant were included. In these patients, underlying disease, intraocular pressure change, and the number of injections were analyzed. @*Results@#A total of 1,168 injections of 473 eyes (439 patients) were enrolled in the study. The mean number of injections was 2.5 per eye. The mean age was 61.4 ± 11.3 years. The complications requiring an additional surgical procedure occurred in six (0.5%) injections. Of them, four, one, and one eyes showed uveitis, diabetic macular edema, and branch retinal vein occlusion, respectively. Surgical management was performed to control the increased intraocular pressure in two eyes, inappropriate implant location in two eyes, scleral wound leakage in one eye, and retinal detachment in one eye. The incidence of severe complications requiring surgical management was high in cases with a history of previous vitrectomy (p = 0.007, Fisher’s exact test) and uveitis (p = 0.007, Fisher’s exact test). @*Conclusions@#Severe complications requiring surgical management occurred in 0.5% of cases (six cases) after intravitreal dexamethasone implant injections. These complications were related to a history of previous vitrectomy and uveitis. Five eyes recovered to favorable visual function after surgery, with the exception of one eye with retinal detachment.
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Purpose@#To report a case of Behçet’s disease presenting as a macular hole with exudative retinal detachment and an examination of its mechanism.Case summary: A 19-year-old woman presented with decreased visual acuity in her right eye for a month. The visual acuity of the right eye was finger count. Inflammation was evident in the anterior chamber cells and vitreous. Optical coherence tomography revealed a macular hole with retinal detachment. Retinal vasculitis was observed in fluorescein angiography imagery. Vasculitis was well controlled with administration of 1 mg per kg oral prednisolone. Vitrectomy and internal limiting membrane (ILM) peeling were performed with ILM flap creation. The macular hole was closed after the surgery. Behçet’s disease was diagnosed based on a manifestation of genital and oral ulcers during tapering of prednisolone. Subcutaneous adalimumab has been used to control uveitis due to repeated relapse. @*Conclusions@#This is a case of Behçet’s disease initially presenting as macular hole retinal detachment. Uveitis such as that occurring with Behçet’s disease should be considered if the macular hole retinal detachment is noticed in a young patient without posterior staphyloma.
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Purpose@#To report a case of Behçet’s disease presenting as a macular hole with exudative retinal detachment and an examination of its mechanism.Case summary: A 19-year-old woman presented with decreased visual acuity in her right eye for a month. The visual acuity of the right eye was finger count. Inflammation was evident in the anterior chamber cells and vitreous. Optical coherence tomography revealed a macular hole with retinal detachment. Retinal vasculitis was observed in fluorescein angiography imagery. Vasculitis was well controlled with administration of 1 mg per kg oral prednisolone. Vitrectomy and internal limiting membrane (ILM) peeling were performed with ILM flap creation. The macular hole was closed after the surgery. Behçet’s disease was diagnosed based on a manifestation of genital and oral ulcers during tapering of prednisolone. Subcutaneous adalimumab has been used to control uveitis due to repeated relapse. @*Conclusions@#This is a case of Behçet’s disease initially presenting as macular hole retinal detachment. Uveitis such as that occurring with Behçet’s disease should be considered if the macular hole retinal detachment is noticed in a young patient without posterior staphyloma.
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Tofacitinib, a Janus kinase inhibitor, was developed for the treatment of rheumatoid arthritis. Recently, it has been associated with an increased change in arthritis development in patients with diabetes. Herein, we evaluated the pharmacokinetics of tofacitinib after intravenous (10 mg/kg) and oral (20 mg/kg) administration to rats with streptozotocin-induced diabetes mellitus and control rats. Following intravenous administration of tofacitinib to rats with streptozotocin-induced diabetes mellitus, area under the plasma concentration-time curve from time zero to infinity of tofacitinib was significantly smaller (33.6%) than that of control rats. This might be due to the faster hepatic intrinsic clearance (112%) caused by an increase in the hepatic cytochrome P450 (CYP) 3A1(23) and the faster hepatic blood flow rate in rats with streptozotocin-induced diabetes mellitus than in control rats. Following oral administration, area under the plasma concentration-time curve from time zero to infinity of tofacitinib was also significantly smaller (55.5%) in rats with streptozotocin-induced diabetes mellitus than that in control rats. This might be due to decreased absorption caused by the higher expression of P-glycoprotein and the faster intestinal metabolism caused by the higher expression of intestinal CYP3A1(23), which resulted in the decreased bioavailability of tofacitinib (33.0%) in rats with streptozotocin-induced diabetes mellitus. In summary, our findings indicate that diabetes mellitus affects the absorption and metabolism of tofacitinib, causing faster metabolism and decreased intestinal absorption in rats with streptozotocin-induced diabetes mellitus.
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PURPOSE: To compare non-cycloplegic and cycloplegic refractive errors and evaluate the utility of cycloplegia in Korean children and young adolescents.METHODS: An anterospective study including 406 outpatients was conducted from September 2015 to December 2017. Pre and post-cycloplegic refractive errors for both eyes were measured using Ocucyclo® and Mydrin P® with an auto-refractor. Patients were divided into different groups according to age: group 1 (< 4 years), group 2 (4–6 years), group 3 (6–8 years), group 4 (8–10 years) and group 5 (< 20 years).RESULTS: A total of 203 patients were studied. Standard deviation (sphere post-pre) was 1.26 ± 1.02 diopters significant in all age groups (p < 0.05). The mean difference decreased with increasing age (r = 0.207, p < 0.05), however, 9% of group with age greater than 10 years old still had manifest refraction-cycloplegic refraction (MR-CR) difference greater than 2 diopters. There were no significant cylindrical or axial component value difference before and after cycloplegia (p = 0.071). Significantly greater MR-CR differences were observed in hypermetropes ≥ 6 years old and myopes ≤8 years old (p < 0.05). The prevalence of pre-cycloplegic eyes with anisometria was 22.6% and 32.6%, a total of 7.39% regressed after cycloplegia (p > 0.05).CONCLUSIONS: After CR hyperopic shift was observed in all age groups. In patients with age greater than 10 years old, although statistically not significant, anisometropia and pseudomyopia still existed. Thus cycloplegic refraction should be performed in young adolescent to precisely measure and correct refractive error and avoid overcorrection.
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Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans (Aa), Tannerella forsythia (Tf), Prevotella intermedia (Pi), and Fusobacterium nucleatum (Fn) are major periodontal pathogens. Lipopolysaccharides (LPSs) from periodontal bacteria play an important role in periodontal pathogenesis by stimulating host cells to produce inflammatory cytokines. In this study, highly pure LPSs from the five major periodontopathogens were prepared, and their monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α)-inducing activities were compared in human umbilical vein endothelial cells (HUVECs) and THP-1 macrophagic cells, respectively. In HUVECs, LPSs from Aa and Fn were potent stimulators for MCP-1 induction; however, LPSs from Pg, Pi, and Tf were much weaker MCP-1 inducers. In THP-1 cells, LPSs from Pg, Aa, and Fn were relatively strong inducers of TNF-α, whereas LPSs from Pi and Tf produced little activity. The Toll-like receptor (TLR)2/TLR4 dependency of various LPSs was also determined by measuring NF-κB reporter activity in TLR2- or TLR4-expressing 293 cells. LPSs from Aa, Fn, and Tf stimulated only TLR4; however, LPSs from Pg and Pi stimulated both TLR2 and TLR4. These results suggest that LPSs from major periodontal bacteria differ considerably in their cell-stimulating activity.
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PURPOSE: This study examined the effects of spinal stabilization exercises using visual feedback on the gross motor function and balance of the sitting posture in children with cerebral palsy.METHODS: The subjects were 18 children with cerebral palsy aged 8–15 years in the I–III stages of the Gross Motor Function Classification System. The subjects were divided into an experimental group (n=9) and control group (n=9). The experimental group was treated with 30 minutes of neurodevelopmental treatment and 20 minutes of spinal stabilization exercises using visual feedback. The control group was treated with 30 minutes of neurodevelopmental treatment and 20 minutes of spinal stabilization exercises without visual feedback. Both groups participated in the experiment twice a week for eight weeks. The Gross Motor Function Measurement was performed to evaluate the changes between pre- and the post-intervention in gross motor function. The Seated Limit of Stability Surface Area was measured to evaluate the changes in trunk balance.RESULTS: Both experimental and control groups showed a significant increase in the gross motor function and trunk balance (p<0.05). The experimental group showed a significant increase in gross motor function compared to the control group (p<0.05). The experimental group showed a significant increase in the dynamic trunk balance in all directions when measuring the Seated Limit of Stability Surface Area (p<0.05).CONCLUSION: Spinal stabilization exercises using visual feedback for the neurodevelopmental treatment of children with cerebral palsy can improve their gross motor function and trunk balance when in a sitting posture more effectively.
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Niño , Humanos , Parálisis Cerebral , Clasificación , Ejercicio Físico , Retroalimentación Sensorial , PosturaRESUMEN
Breast cancer is currently the most prevalent cancer in women, and its incidence increases every year. Azole antifungal drugs were recently found to have antitumor efficacy in several cancer types. They contain an imidazole (clotrimazole and ketoconazole) or a triazole (fluconazole and itraconazole) ring. Using human breast adenocarcinoma cells (MCF-7 and MDA-MB-231), we evaluated the effects of azole drugs on cell proliferation, apoptosis, cell cycle, migration, and invasion, and investigated the underlying mechanisms. Clotrimazole and ketoconazole inhibited the proliferation of both cell lines while fluconazole and itraconazole did not. In addition, clotrimazole and ketoconazole inhibited the motility of MDA-MB-231 cells and induced G₁-phase arrest in MCF-7 and MDA-MB-231 cells, as determined by cell cycle analysis and immunoblot data. Moreover, Transwell invasion and gelatin zymography assays revealed that clotrimazole and ketoconazole suppressed invasiveness through the inhibition of matrix metalloproteinase 9 in MDA-MB-231 cells, although no significant changes in invasiveness were observed in MCF-7 cells. There were no significant changes in any of the observed parameters with fluconazole or itraconazole treatment in either breast cancer cell line. Taken together, imidazole antifungal drugs showed strong antitumor activity in breast cancer cells through induction of apoptosis and G₁ arrest in both MCF-7 and MDA-MB-231 cells and suppression of invasiveness via matrix metalloproteinase 9 inhibition in MDA-MB-231 cells. Imidazole drugs have well-established pharmacokinetic profiles and known toxicity, which can make these generic drugs strong candidates for repositioning as antitumor therapies.