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Felodipine has proven to be effective as an atherosclerosis therapy because it increases blood flow to the vessel wall. However, the poor solubility, low bioavailability, and hepatic first-pass metabolism of oral felodipine compromise its therapeutic effectiveness. The study's goal is to create a nasal pH-sensitive hydrogel of felodipine-loaded invasomes (IPHFI) that will improve felodipine's release, permeation, bioavailability, and efficacy as a potential diabetes-associated atherosclerosis therapy. According to the pre-formulation study, the felodipine-loaded invasomes formulation composed of phospholipid (3%w/v), cholesterol (0.16%w/v), ethanol (3%v/v) and cineole (1%v/v) was chosen as the optimum formulation. The optimum formulation was characterized in vitro and then mixed with a mixture of chitosan and glyceryl monooleate to make the IPHFI formulation. The IPHFI formulation enhanced the release and permeation of felodipine by 2.99 and 3-fold, respectively. To assess the efficacy and bioavailability of the IPHFI formulation, it was studied in vivo using an experimental atherosclerosis rat model. Compared to oral free felodipine, the nasal administration of the IPHFI formulation increased the bioavailability by 3.37-fold and decreased the serum cholesterol, triglycerides, LDL, and calcification score by 1.56, 1.53, 1.80, and 1.18 ratios, respectively. Thus, nasal IPHFI formulation may represent a promising diabetes-associated atherosclerosis therapy.
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Aterosclerose , Disponibilidade Biológica , Liberação Controlada de Fármacos , Felodipino , Felodipino/administração & dosagem , Felodipino/farmacocinética , Felodipino/química , Animais , Aterosclerose/tratamento farmacológico , Masculino , Ratos , Ratos Sprague-Dawley , Hidrogéis/química , Quitosana/química , Bloqueadores dos Canais de Cálcio/farmacocinética , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/química , Diabetes Mellitus Experimental/tratamento farmacológico , Concentração de Íons de Hidrogênio , Solubilidade , Fosfolipídeos/química , Complicações do Diabetes/tratamento farmacológico , Colesterol/química , Portadores de Fármacos/químicaRESUMO
PURPOSE: Although pivotal trials have demonstrated efficacy of anti-vascular endothelial growth factor therapy in neovascular age-related macular degeneration, there is a paucity of clinical data about the long-term (>5 years) treatment. METHODS: Retrospective analysis of all patients with neovascular age-related macular degeneration who were actively treated, had received >40 anti-vascular endothelial growth factor injections, and were followed for ≥5 years. Snellen-corrected visual acuity, initial drug choice, and times elapsed between treatments were collected. Rates of endophthalmitis and outcomes of submacular hemorrhage were also evaluated. RESULTS: A total of 88 patients (162 eyes) met the inclusion criteria: the average patient age was 86.3 years with an average follow-up period of 7.6 years. The average total number of injections per eye was 69 (18.0 SD); a total of 11,208 injections were given throughout the study period, and 6 cases (0.05%) of endophthalmitis were observed. Overall, there was a clinical and statistical difference in average Snellen-corrected visual acuity at Injections #2,#3, #4, #5, #6, #10, and #20, as compared with baseline ( P = 0.03, P < 0.01, P = 0.02, P < 0.01, P = 0.01, P = 0.01, P < 0.01, respectively). Patients in the Snellen-corrected visual acuity subgroup 20/20 to 20/40 maintained vision until injection #30. Seven eyes experienced a visually significant submacular hemorrhage. CONCLUSION: This neovascular age-related macular degeneration cohort received on average eight anti-vascular endothelial growth factor injections per year for approximately 8 years; eyes with good (≥20/40) initial baseline vision maintained their visual acuity, whereas those with worse Snellen-corrected visual acuity (≤20/50) had a robust initial improvement that diminished with time. Most patients were maintained on the same initial drug of choice and the rate of endophthalmitis was low.
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Endoftalmite , Degeneração Macular , Degeneração Macular Exsudativa , Humanos , Pré-Escolar , Idoso de 80 Anos ou mais , Criança , Inibidores da Angiogênese/uso terapêutico , Ranibizumab/uso terapêutico , Bevacizumab/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento Endotelial , Estudos Retrospectivos , Injeções Intravítreas , Hemorragia Retiniana/tratamento farmacológico , Degeneração Macular/tratamento farmacológico , Endoftalmite/tratamento farmacológico , Endoftalmite/epidemiologia , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/tratamento farmacológico , Resultado do TratamentoRESUMO
PURPOSE: To report on macular hole repair in macular telangiectasia type 2 (MacTel2). DESIGN: Global, multicenter, retrospective case series. PARTICIPANTS: Patients undergoing surgery for MacTel2-associated full-thickness macular hole (MTMH). METHODS: Standardized data collection sheet distributed to all surgeons. MAIN OUTCOME MEASURES: Anatomic closure and visual outcomes of MTMH. RESULTS: Sixty-three surgeries in 47 patients with MTMH were included from 30 surgeons. Mean age was 68.1 years, with 62% female, 72% White, 21% East or South Asian, 2% African American, and 2% Hispanic or Latino. Procedures included 34 internal limiting membrane (ILM) peeling alone, 22 ILM flaps, 5 autologous retinal transplantations (ARTs), 1 retinotomy, and 1 subretinal bleb. For ILM peeling, preoperative visual acuity (VA) was 0.667 ± 0.423 logarithm of the minimum angle of resolution (logMAR). Minimum hole diameter (MHD) was 305.5 ± 159.4 µm (range, 34-573 µm). Sixteen of 34 ILM peels (47%) resulted in MTMH closure. At postoperative month 6, VA was stable at 0.602 ± 0.516 logMAR (P = 0.65). VA improved by at least 2 lines in 43% and at least 4 lines in 24%. For ILM flaps, preoperative VA was 0.878 ± 0.552 logMAR. MHD was 440.8 ± 175.5 µm (range, 97-697 µm), which was significantly larger than for ILM peels (P < 0.01). Twenty of 22 ILM flaps (90%) resulted in MTMH closure, which was significantly higher than for ILM peels (P < 0.01). At postoperative month 6, VA improved to 0.555 ± 0.405 logMAR (P < 0.05). VA improved by at least 2 lines in 56% and at least 4 lines in 28%. For ARTs, preoperative VA was 1.460 ± 0.391 logMAR. MHD was 390.2 ± 203.7 µm (range, 132-687 µm). All 5 ARTs (100%) resulted in MTMH closure. At postoperative month 6, VA was stable at 1.000 ± 0.246 logMAR (P = 0.08). Visual acuity improved at least 2 lines in 25%. CONCLUSIONS: Surgical closure of macular holes improved VA in 57% of MTMHs. Internal limiting membrane flaps achieved better anatomic and functional outcomes than ILM peeling alone. Autologous retinal transplantation may be an option for refractory MTMHs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Membrana Epirretiniana , Perfurações Retinianas , Telangiectasia Retiniana , Humanos , Feminino , Idoso , Masculino , Vitrectomia/métodos , Estudos Retrospectivos , Retina , Telangiectasia Retiniana/diagnóstico , Telangiectasia Retiniana/cirurgia , Telangiectasia Retiniana/complicações , Membrana Basal/cirurgia , Tomografia de Coerência Óptica , Resultado do Tratamento , Membrana Epirretiniana/cirurgiaRESUMO
BACKGROUND AND AIM: Uremic pruritus (UP) is one of the most distressing symptoms in hemodialysis (HD) patients. Subclinical hypothyroidism (SCH) is a biochemical condition with high prevalence in HD patients. The present multicentric study aimed to assess the relationship between UP and SCH in HD patients. METHODS: The present cross-sectional study included 328 HD patients. All patients were submitted to careful history through clinical examination and standard laboratory assessment. Pruritis was evaluated using the pruritis visual analog scale (VAS). Patients were diagnosed with SCH if they had TSH levels above the upper limit of the normal reference range in association with normal free thyroxine (FT4) levels. RESULTS: Among the studied patients, there were 196 patients (59.8 %) with UP. Comparison between patients with UP and patients without revealed that patients in the former group had significantly longer HD duration (median (IQR): 47.5 (27.0-72.5) versus 36.0 (23.0-50.5) months, p < 0.001) and lower Kt/v (median (IQR): 1.4 (1.09-1.7) versus 1.54 (1.12-1.91), p = 0.009). Moreover, they had significantly higher ferritin (median (IQR): 653.0 (526.0-800.0) versus 628.0 (470.8- 716.0) ng/mL), hsCRP (median (IQR): 12.0 (8.0-14.0) versus 8.0 (6.0-9.0) mg/dL, p < 0.001) and TSH levels (median (IQR): 4.34 (1.98-5.2) versus 3.34 (1.9-4.85) µIU/ml) with a significantly higher frequency of SCH (45.9 % versus 28.8 %, p = 0.002). Logistic regression analysis identified hemodialysis duration (OR (95%) CI): 1.02 (1.009-1.028), p < 0.001), ferritin levels (OR (95% CI): 1.002 (1.001-1.003), p < 0.001), and SCH (OR (95% CI): 0.54 (0.32-0.89), p = 0.016) as significant predictors of UP. CONCLUSION: The present study suggested a possible link between SCH and the development of UP in HD patients.
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Hipotireoidismo , Tireotropina , Humanos , Estudos Transversais , Hipotireoidismo/complicações , Hipotireoidismo/diagnóstico , Hipotireoidismo/epidemiologia , Prurido/diagnóstico , Prurido/epidemiologia , Prurido/etiologia , Diálise Renal/efeitos adversos , Ferritinas , TiroxinaRESUMO
PURPOSE: To report a case of a patient who suffered a full thickness macular hole (FTMH) due to the accidental utilization of the selective laser trabeculoplasty (SLT) mode of a dual mode laser. METHOD: Case report. RESULTS: A 69-year-old woman experienced vision loss in her left eye immediately after undergoing attempted Neodymium:yttrium-aluminum-garnet (Nd:YAG) capsulotomy using a Nd:YAG-SLT laser system. Post-injury visual acuity was 20/25 and 20/800 in the right and left eyes, respectively. Ophthalmic exam and multimodal imaging revealed multiple macular hemorrhages and an irregular FTMH. The patient required multiple surgeries including an autologous retinal transplant to achieve hole closure. CONCLUSIONS: Macular hole formation is a devastating consequence of inadvertent use of the SLT mode when performing a Nd:YAG laser capsulotomy with a Nd:YAG-SLT laser system. We emphasize the importance of ensuring the correct mode is selected for treatment to minimize the risk of retinal damage and permanent vision loss.
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Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder caused by antigen-specific T cells and antiplatelet autoantibodies that inhibit platelet production in the bone marrow or destroy platelets in the spleen. ITP is a form of autoimmunity and is closely associated with inflammation. Corticosteroids are the first-line therapy for ITP, with a total response rate of 53-80%. However, corticosteroid therapy is associated with significant side effects and is often ineffective in patients with corticosteroid-resistant or -intolerant disease. Eltrombopag has been validated as a second-line option in ITP therapy. Despite several studies demonstrating the efficacy and safety of Eltrombopag in immune thrombocytopenia patients, the prevalence of Eltrombopag-induced acute kidney injury has been observed. This case report describes a patient who experienced acute kidney injury during Eltrombopag therapy. A sudden increase in serum creatinine to 6.7 mg/dL and metabolic acidosis occurred after eight weeks of Eltrombopag. The patient's renal failure had worsened, proteinuria was detected, and emergency hemodialysis was initiated. With vigilant kidney function screening and prompt treatment, the patient's renal function improved remarkably following cessation of Eltrombopag and initiation of hemodialysis. This case highlights the importance of comprehensive medication history-taking and vigilant kidney function screening in patients receiving Eltrombopag.
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This paper studies the effect of the laser melting process (LMP) on the microstructure and hardness of a new modified AlCuMgMn alloy with zirconium (Zr) and Yttrium (Y) elements. Homogenized (480 °C/8 h) alloys were laser-surface-treated at room temperature and a heating platform with in situ heating conditions was used in order to control the formed microstructure by decreasing the solidification rate in the laser-melted zone (LMZ). Modifying the AlCuMgMn alloy with 0.4 wt% Zr and 0.6 wt% Y led to a decrease in grain size by 25% with a uniform grain size distribution in the as-cast state due to the formation of Al3(Y, Zr). The homogenization dissolved the nonequilibrium intermetallic phases into the (Al) matrix and spheroidized and fragmentized the equilibrium phase's particles, which led to the solidification of the crack-free LM zone with a nonuniform grain structure. The microstructure in the LMZ was improved by using the in situ heating approach, which decreased the temperature gradient between the BM and the melt pool. Two different microstructures were observed: ultrafine grains at the boundaries of the melted pool due to the extremely high concentration of optimally sized Al3(Y, Zr) and fine equiaxed grains at the center of the LMZ. The combination of the presence of ZrY and applying a heating platform during the LMP increased the hardness of the LMZ by 1.14 times more than the hardness of the LMZ of the cast AlCuMgMn alloy.
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Erythropoietin (EPO) resistance is frequently reported in hemodialysis (HD) patients. Metabolic syndrome (MetS) is a common biochemical condition that comprises central obesity, dyslipidemia, hypertension, and hyperglycemia. The present study aimed to assess the relation between MetS and EPO resistance in HD patients. The present multicentric study included 150 patients with EPO resistance and 150 patients without EPO resistance. Short-acting EPO resistance was diagnosed if the erythropoietin resistance index is ≥1.0 IU/kg/gHb. Comparison between patients with EPO resistance and patients without resistance revealed that the former group had significantly higher body mass index, lower hemoglobin levels, lower albumin levels, higher ferritin levels, and higher high-sensitivity C-reactive protein (hsCRP) levels. In addition, patients in the EPO resistance group had significantly higher frequency of MetS (75.3% vs 38.0%, p < 0.001) and higher number of MetS components (2.7 ± 1.3 vs 1.8 ± 1.6, p < 0.001). Multivariate logistic regression analysis identified lower albumin levels (OR (95% CI): 0.072 (0.016-0.313), p < 0.001), higher ferritin levels (OR (95% CI): 1.05 (1.033-1.066), p< 0.001), higher hsCRP levels (OR (95% CI): 1.041 (1.007-1.077), p = 0.018), and MetS (OR (95% CI): 36.68 (2.893-465.05), p = 0.005) as predictors of EPO resistance in the studied patients. The present study identified MetS as a predictor of EPO resistance in HD patients. Other predictors include serum ferritin, hsCRP, and albumin levels.
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In this work, 2 mm thick medium-Mn austenitic stainless steel (MMn-SS) plates were joined with austenitic NiCr stainless steel (NiCr-SS) and low-carbon steel (LCS) using the gas tungsten arc welding technique. A precise adjustment of the welding process parameters was conducted to achieve high-quality dissimilar joints of MMn-SS with NiCr-SS and LCS. The microstructural evolution was studied using laser scanning confocal and electron microscopes. Secondary electron imaging and electron backscatter diffraction (EBSD) techniques were intensively employed to analyze the fine features of the weld structures. The mechanical properties of the joints were evaluated by uniaxial tensile tests and micro-indentation hardness (HIT). The microstructure of the fusion zone (FZ) in the MMn-SS joints exhibited an austenitic matrix with a small fraction of δ-ferrite, ~6%. The tensile strength (TS) of the MMn-SS/NiCr-SS joint is significantly higher than that of the MMn-SS/LCS joint. For instance, the TSs of MMn-SS joints with NiCr-SS and LCS are 610 and 340 MPa, respectively. The tensile properties of MMn-SS/LCS joints are similar to those of BM LCS, since the deformation behavior and shape of the tensile flow curve for that joint are comparable with the flow curve of LCS. The HIT measurements show that the MMn-SS/NiCr-SS joint is significantly stronger than the MMn-SS/LCS joint since the HIT values are 2.18 and 1.85 GPa, respectively.
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BACKGROUND: The CLOSE study group proposes an updated surgical classification for large macular holes based on a systematic review of new treatments. Recently, many new techniques have been introduced to treat large full-thickness macular holes (FTMH); although the indications are not clear. An updated surgical classification is needed to help surgical decision-making. METHODS: We gathered published series by the CLOSE Study Group members and from literature search until June 2021. Techniques included: internal limiting membrane peeling (ILM peeling), ILM flaps, macular hydrodissection (macular hydro), human amniotic membrane graft (hAM), and autologous retinal transplantation (ART). Within each technique, chi-square test assessed association between the minimal linear diameter (MLD) (in µm) and closure rate; the postoperative best-corrected visual acuity (BCVA) gains were compared among groups. RESULTS: Data extraction included 31 published articles: total of 1135 eyes. Eyes were divided into the following groups: ILM peel (n: 683), ILM Flap (n: 233), macular hydrodissection (n: 64), hAM (n: 59), and ART (n: 96). The initial BCVA and size were heterogenous between the groups. ILM peel showed the best results in large FTMH ≤ 535 µm (closure rate 96.8%); adjusted mean BCVA: 0.49 (LogMAR) with a statistical difference among groups. Large FTMH between 535 and 799 µm: ILM flap technique showed better results (closure rate 99.0%); adjusted mean BCVA: 0.67(LogMAR); also with a statistical difference. For large FTMH ≥ 800 µm more invasive techniques are required. Use of hAM, macular hydrodissection and ART showed higher closure rates for this category (100%, 83.3% and 90.5% respectively), and adjusted mean BCVA varied from 0.76 to 0.89. Although there was no statistical difference between those techniques for this group due to the smaller number of cases. CONCLUSIONS: The CLOSE study group demonstrated the potential usefulness of a new surgical classification for large FTMHs and propose OCT biomarkers for use in clinical practice and future research. This new classification demonstrated that Large (400-550 µm) and X-Large (550-800 µm) holes can be treated highly successfully with ILM peel and ILM flap techniques, respectively. Further studies are necessary for the larger FTMHs (XX-Large and Giant), using the CLOSE classification, in order to determine which technique is better suited for each hole size and characteristics.
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Membrana Epirretiniana , Perfurações Retinianas , Humanos , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/etiologia , Perfurações Retinianas/cirurgia , Membrana Epirretiniana/diagnóstico , Membrana Epirretiniana/cirurgia , Membrana Epirretiniana/complicações , Retina , Vitrectomia , Retalhos CirúrgicosRESUMO
BACKGROUND AND AIM: Chronic kidney disease (CKD) is characterized by persistent lowgrade inflammation. Soluble CD14 (sCD14) is involved in many pathological conditions, including inflammation and atherosclerosis. The present study aimed to assess the relationship between sCD14 levels, subclinical atherosclerosis (SCA), inflammation and mortality in Egyptian hemodialysis (HD) patients. PATIENTS AND METHODS: The present longitudinal study included 62 HD patients. All patients were submitted to careful history taking, thorough clinical examination and laboratory assessment for high-sensitivity C-reactive protein (hsCRP) and sCD14. Carotid intima-media thickness (CIMT) was also assessed. Patients were followed for a maximum of 18 months. The primary outcome is patients' mortality. Data were statistically analyzed using standard descriptive, comparative, correlative and regression methods. RESULTS: The present study was conducted on 62 HD patients. They comprised 34 males and 28 females with an age of 54.6 ± 9.0 years. At the end of follow-up, 12 patients (19.4 %) died. It was shown that survivors had significantly lower hsCRP levels (104.2 ± 38.2 versus 134.1 ± 15.3 mg/dL, p < 0.001), lower sCD14 levels (32.7 ± 10.3 versus 47.4 ± 18.4 µg/mL, p = 0.02) and lower CIMT (1.32 ± 0.5 versus 1.5 ± 0.2 mm, p = 0.049). sCD14 levels were significantly correlated with hsCRP (r = 0.4, p = 0.001) and CIMT (r = 0.31, p = 0.013). Multivariate analysis identified HD duration [HR (95% CI): 1.02 (1.0-1.04), p = 0.021] and sCD14 levels [HR (95% CI): 1.06 (1.0-1.12), p = 0.026] as significant predictors of patients' survival. CONCLUSIONS: sCD14 levels in this cohort of HD patients are well-correlated with hsCRP levels and CIMT. In addition, they are significant predictors of patients' mortality.
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Aterosclerose , Receptores de Lipopolissacarídeos , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Proteína C-Reativa/metabolismo , Estudos Longitudinais , Espessura Intima-Media Carotídea , Biomarcadores , Inflamação , Diálise Renal/efeitos adversos , Aterosclerose/diagnósticoRESUMO
PURPOSE: To present representative cases of the most common complications associated with an autologous retinal transplant (ART) for macular hole repair. METHODS: A retrospective, consecutive case series on patients who underwent an ART by a single provider (Tamer H. Mahmoud). RESULTS: Four cases were included in this review. Each suffered an ART-specific complication, including graft displacement and dislocation, sub-ART perfluoron, and a delayed proliferative vitreoretinopathy-associated retinal detachment. CONCLUSION: Because more surgeons use ART to treat atypical macular holes, an adequate understanding of surgery-specific complications and techniques to treat those complications is increasingly necessary.
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Descolamento Retiniano , Perfurações Retinianas , Humanos , Estudos Retrospectivos , Vitrectomia/efeitos adversos , Vitrectomia/métodos , Acuidade Visual , Retina/transplante , Descolamento Retiniano/cirurgia , Descolamento Retiniano/complicações , Perfurações Retinianas/cirurgia , Perfurações Retinianas/complicações , Complicações Pós-Operatórias/cirurgiaRESUMO
Patients with neurological comorbidities are more likely to develop severe COVID-19. We aimed to detect the outcomes of COVID-19 patients with spontaneous intracerebral hemorrhage comorbidity and the role of enoxaparin in decreasing the mortality rate in these cases, even though enoxaparin is a potential cause of intracerebral hemorrhage. The patients were checked on to detect surveillance outcomes, the relationship between mortality and patient characteristics, and the relationship between enoxaparin and study outcomes. Chest condition and GCS improved in 67.9% of participants. Hematoma course increased in 49.1%. Midline-shift, brain-edema, and COVID symptoms improved in 67.9%. There was a non-significant difference in mortality regarding age and gender. There was a significant difference in mortality regarding treatment with enoxaparin; 75% of the patients who did not receive enoxaparin died. 92.6% of the patients who showed decreases in hematoma course were administered enoxaparin. 76.9% of the patients who showed increases in hematoma-course were administered enoxaparin. Most of the patients who were admitted to the neurosurgical unit with spontaneous intracerebral hemorrhage acquired the COVID-19 infection. Most of the cases included in this study did not progress to severe cases. The dying patients showed deterioration in both neurological and COVID-19 symptoms. The anticoagulant properties of enoxaparin given earlier before and throughout the infection can considerably reduce mortality in COVID-19 individuals with spontaneous intracerebral hemorrhage. It is recommended to use enoxaparin for cases with spontaneous intracerebral hemorrhage and COVID-19 regardless of hematoma size because the rate of improvement was greater than the mortality rate after using enoxaparin in this study.
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BACKGROUND AND OBJECTIVE: To describe an under-recognized complication in the surgical management of dense, nonclearing vitreous hemorrhage, specifically, the development of iatrogenic retinal breaks as a result of cutter-associated traction. STUDY DESIGN/PATIENTS AND METHODS: Review of surgical cases with cutter-associated traction from chronic vitreous hemorrhage (CATCH). RESULTS: Cutter-associated traction from chronic vitreous hemorrhage is a commonly encountered surgical entity that may result in complications such as iatrogenic retinal breaks, including giant retinal tears. These complications can be minimized or potentially avoided through the use of open sclerotomies or potentially mixed-gauge vitrectomy. CONCLUSION: Careful surgical planning in cases of dense or chronic vitreous hemorrhage is required to prevent cutter-associated tractional retinal breaks. [Ophthalmic Surg Lasers Imaging Retina 2022;53:584-585.].
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Descolamento Retiniano , Perfurações Retinianas , Seguimentos , Humanos , Doença Iatrogênica/prevenção & controle , Descolamento Retiniano/cirurgia , Perfurações Retinianas/etiologia , Estudos Retrospectivos , Tração/efeitos adversos , Vitrectomia/métodos , Hemorragia Vítrea/etiologia , Hemorragia Vítrea/prevenção & controle , Hemorragia Vítrea/cirurgiaRESUMO
The oral delivery of diclofenac sodium (DNa), a non-steroidal analgesic, anti-inflammatory drug, is associated with various gastrointestinal side effects. The aim of the research was to appraise the potential of transdermal delivery of DNa using bilosomes as a vesicular carrier (BSVC) in inflamed paw edema. DNa-BSVCs were elaborated using a thin-film hydration technique and optimized using a 31.22 multilevel categoric design with Design Expert® software 10 software (Stat-Ease, Inc., Minneapolis, MI, USA). The effect of formulation variables on the physicochemical properties of BSVC, as well as the optimal formulation selection, was investigated. The BSVCs were evaluated for various parameters including entrapment efficiency (EE%), vesicle size (VS), zeta potential (ZP) and permeation studies. The optimized BSVC was characterized for in vitro release, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and incorporated into hydrogel base. The optimized DNa-BSVC gel effectiveness was assessed in vivo using carrageenan-induced paw edema animal model via cyclooxygenase 2 (COX-2), interleukin 6 (IL-6), Hemooxygenase 1 (HO-1) and nuclear factor-erythroid factor2-related factor 2 (Nfr-2) that potentiate anti-inflammatory and anti-oxidant activity coupled with histopathological investigation. The resulting vesicles presented VS from 120.4 ± 0.65 to 780.4 ± 0.99 nm, EE% from 61.7 ± 3.44 to 93.2 ± 2.21%, ZP from -23.8 ± 2.65 to -82.1 ± 12.63 mV and permeation from 582.9 ± 32.14 to 1350.2 ± 45.41 µg/cm2. The optimized BSVCs were nano-scaled spherical vesicles with non-overlapped bands of their constituents in the FTIR. Optimized formulation has superior skin permeability ex vivo approximately 2.5 times greater than DNa solution. Furthermore, histological investigation discovered that the formed BSVC had no skin irritating properties. It was found that DNa-BSVC gel suppressed changes in oxidative inflammatory mediators (COX-2), IL-6 and consequently enhanced Nrf2 and HO-1 levels. Moreover, reduction of percent of paw edema by about three-folds confirmed histopathological alterations. The results revealed that the optimized DNa-BSVC could be a promising transdermal drug delivery system to boost anti-inflammatory efficacy of DNa by enhancing the skin permeation of DNa and suppressing the inflammation of rat paw edema.
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The Salicornia L. has been considered one of the most taxonomically challenging genera due to high morphological plasticity, intergradation between related species, and lack of diagnostic features in preserved herbarium specimens. In the United Arab Emirates (UAE), only one species of this genus, Salicornia europaea, has been reported, though investigating its identity at the molecular level has not yet been undertaken. Moreover, based on growth form and morphology variation between the Ras-Al-Khaimah (RAK) population and the Umm-Al-Quwain (UAQ) population, we suspect the presence of different species or morphotypes. The present study aimed to initially perform species identification using multilocus DNA barcode markers from chloroplast DNA (cpDNA) and nuclear ribosomal DNA (nrDNA), followed by the genetic divergence between two populations (RAK and UAQ) belonging to two different coastal localities in the UAE. The analysis resulted in high-quality multilocus barcode sequences subjected to species discrimination through the unsupervised OTU picking and supervised learning methods. The ETS sequence data from our study sites had high identity with the previously reported sequences of Salicornia persica using NCBI blast and was further confirmed using OTU picking methods viz., TaxonDNAs Species identifier and Assemble Species by Automatic Partitioning (ASAP). Moreover, matK sequence data showed a non-monophyletic relationship, and significant discrimination between the two populations through alignment-based unsupervised OTU picking, alignment-free Co-Phylog, and alignment & alignment-free supervised learning approaches. Other markers viz., rbcL, trnH-psbA, ITS2, and ETS could not distinguish the two populations individually, though their combination with matK (cpDNA & cpDNA+nrDNA) showed enough population discrimination. However, the ITS2+ETS (nrDNA) exhibited much higher genetic divergence, further splitting both the populations into four haplotypes. Based on the observed morphology, genetic divergence, and the number of haplotypes predicted using the matK marker, it can be suggested that two distinct populations (RAK and UAQ) do exist. Further extensive morpho-taxonomic studies are required to determine the inter-population variability of Salicornia in the UAE. Altogether, our results suggest that S. persica is the species that grow in the present study area in UAE, and do not support previous treatments as S. europaea.
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Chenopodiaceae , Código de Barras de DNA Taxonômico , Chenopodiaceae/genética , Código de Barras de DNA Taxonômico/métodos , DNA de Cloroplastos/genética , DNA de Plantas/genética , Marcadores Genéticos , Filogenia , Análise de Sequência de DNA , Especificidade da Espécie , Aprendizado de Máquina SupervisionadoRESUMO
PURPOSE: To assess the closure rate of large full-thickness macular holes (FTMH) associated with epiretinal membrane (ERM) with a combined epiretinal and internal limiting membrane retracting door flap. METHODS: Retrospective chart review of patients treated at a single tertiary retina practice between January 2017 and November 2019. Individuals with FTMH larger than 400 µm and co-diagnosis of ERM who underwent surgical repair with an ERM flap were included. Patients underwent pars plana vitrectomy with peeling of ERM that was positioned as a retracting door flap to cover the FTMH. Primary outcome was closure rate at 6 months following surgery. Final surgical success rate and visual acuity were secondary outcomes. RESULTS: Among 7 eyes of 7 patients, 6 eyes achieved primary surgical success and final surgical success rate was achieved in all 7 eyes with a large FTMH repaired with ERM flap. The mean minimum linear diameter of the FTMH was 681 µm ± 295. All patients had follow-up greater than 6 months, with a mean duration of 17 months (range 14-23 months). Visual acuity improved from a mean of 0.9 ± 0.3 logMar (20/160) before surgery to 0.3 ± 0.5 logMar (Snellen 20/40), postoperatively. CONCLUSION: Large FTMH with concurrent ERM that are managed with an ERM flap have high single-surgery success rate.