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Tran, J. Q., A. A. Othman, A. Mikulskis, P. Wolstencroft, and J. Elkins, "Pharmacokinetics of daclizumab high-yield process with repeated administration of the clinical subcutaneous regimen in patients with relapsing-remitting multiple sclerosis.", Clinical pharmacology : advances and applications, vol. 8, pp. 9-13, 2016. AbstractWebsite

BACKGROUND: Daclizumab high-yield process (DAC HYP), a humanized immunoglobulin G1 monoclonal antibody specific for the α subunit (CD25) of the high-affinity interleukin-2 receptor, has demonstrated efficacy for treatment of relapsing forms of multiple sclerosis in Phase II and III clinical trials.

OBJECTIVE: To characterize the pharmacokinetics (PK) of DAC HYP following repeated administration of the 150 mg subcutaneous (SC) dose every 4 weeks (q4wk), the proposed clinical regimen in patients with relapsing-remitting multiple sclerosis (RRMS).

METHODS: Twenty-six patients with RRMS received DAC HYP 150 mg SC q4wk for a total of six doses. Serial PK blood samples were collected over the first and last dosing intervals and trough PK samples were collected between these doses. Blood samples for immunogenicity assessment were collected throughout the study. Serum DAC HYP levels and anti-DAC HYP antibodies were characterized using validated immunoassays. PK parameters were estimated using noncompartmental analysis.

RESULTS: DAC HYP showed slow SC absorption with a median time to reach maximum observed concentration (Cmax) value of ~1 week. Steady state was reached by the fourth injection. At steady state, DAC HYP mean serum Cmax, minimum observed concentration (Cmin), and area under the concentration-time curve within a dosing interval (AUCtau) values were 29.1 µg/mL, 14.9 µg/mL, and 638 µg · day/mL, respectively, with intersubject variability of 35%-40%. The AUC accumulation ratio was ~2.5 at steady state. DAC HYP had a long elimination half-life of ~22 days and low apparent clearance (0.274 L/day). Nine patients tested positive for anti-DAC HYP antibodies, with no impact on DAC HYP clearance in this limited data set.

CONCLUSION: The PK of DAC HYP in patients with RRMS are consistent with those previously reported in healthy volunteers. The half-life of ~3 weeks and the low fluctuations in peak and trough concentrations of serum DAC HYP support the once-monthly SC dosing regimen.

Tran, J. Q., A. A. Othman, P. Wolstencroft, and J. Elkins, "Therapeutic protein-drug interaction assessment for daclizumab high-yield process in patients with multiple sclerosis using a cocktail approach.", British journal of clinical pharmacology, vol. 82, issue 1, pp. 160-7, 2016 Jul. AbstractWebsite

AIMS: To characterize the potential effect of daclizumab high-yield process (DAC HYP), a monoclonal antibody that blocks the high-affinity interleukin-2 receptors for treatment of multiple sclerosis, on activity of cytochrome P450 (CYP) enzymes.

METHODS: Twenty patients with multiple sclerosis received an oral cocktail of probe substrates of CYP1A2 (caffeine 200 mg), CYP2C9 (warfarin 10 mg/vitamin K 10 mg), CYP2C19 (omeprazole 40 mg), CYP2D6 (dextromethorphan 30 mg) and CYP3A (midazolam 5 mg) on two sequential occasions: 7 days before and 7 days after subcutaneous administration of DAC HYP 150 mg every 4 weeks for three doses. Serial pharmacokinetic blood samples up to 96 h post dose and 12-h urine samples were collected on both occasions. Area under the curve (AUC) for caffeine, S-warfarin, omeprazole and midazolam, and urine dextromethorphan to dextrorphan ratio were calculated. Statistical analyses were conducted on log-transformed parameters using a linear mixed-effects model.

RESULTS: The 90% confidence intervals (CIs) for the geometric mean ratio (probe substrate with DAC HYP/probe substrate alone) for caffeine AUC from 0-12 h (0.93-1.15), S-warfarin AUC from 0 to infinity (AUC[0-inf]) (0.95-1.06), omeprazole AUC(0-inf) (0.88-1.13) and midazolam AUC(0-inf) (0.89-1.15) were within the no-effect boundary of 0.80-1.25. The geometric mean ratio for urine dextromethorphan to dextrorphan ratio was 1.01, with the 90% CI (0.76-1.34) extending slightly outside the no-effect boundary, likely due to high variability with urine collections and CYP2D6 activity.

CONCLUSIONS: DAC HYP treatment in patients with multiple sclerosis had no effect on CYP 1A2, 2C9, 2C19, 2D6 and 3A activity.

Translator, L. Y., P. Elrefaei, O. Khalifa, and H. H. E. - Abbadi, Recontextualizing Resistance, , Newcastle, Cambridge Scholars Publishing, 2017.
Trebec, D. P., D. Chandra, A. Gramoun, K. Li, J. N. M. Heersche, and M. F. Manolson, "Increased expression of activating factors in large osteoclasts could explain their excessive activity in osteolytic diseases", Journal of cellular biochemistry, vol. 101, no. 1: Wiley Online Library, pp. 205–220, 2007. Abstract
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Trebec, D. P., D. Chandra, A. Gramoun, K. Li, J. N. M. Heersche, and M. F. Manolson, "Increased expression of activating factors in large osteoclasts could explain their excessive activity in osteolytic diseases", Journal of cellular biochemistry, vol. 101, no. 1: Wiley Online Library, pp. 205–220, 2007. Abstract
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Treister, A. D., P. L. Nesper, A. E. Fayed, M. K. Gill, R. G. Mirza, and A. A. Fawzi, "Prevalence of Subclinical CNV and Choriocapillaris Nonperfusion in Fellow Eyes of Unilateral Exudative AMD on OCT Angiography.", Translational vision science & technology, vol. 7, issue 5, pp. 19, 2018. Abstract

Purpose: To determine the prevalence of subclinical choroidal neovascularization (CNV) in fellow eyes of patients with unilateral exudative age-related macular degeneration (AMD) using optical coherence tomography angiography (OCTA) and to quantify choriocapillaris nonperfusion adjacent to CNV.

Methods: We retrospectively reviewed all patients with AMD who underwent OCTA and identified eyes with unilateral exudative AMD. We determined the presence of subclinical CNV on custom en face macular slabs of the outer retina and choriocapillaris and confirmed on cross-sectional scans. Two graders quantified the percent choriocapillaris area of nonperfusion (PCAN) in the entire choriocapillaris slab as well as in the "halo" zone (200 μm) surrounding subclinical and exudative CNV lesions.

Results: Of 140 AMD patients who underwent OCTA, 34 had unilateral exudative AMD, with five of the 34 fellow eyes (14.7%) having subclinical CNV. Compared with PCAN in the entire slab (10.333 ± 4.288%), we found that "halo" PCAN, surrounding CNV, was significantly higher (13.045 ± 5.809%; < 0.001). Further, there was a trend for higher PCAN in exudative CNV eyes (15.267 ± 7.230%) compared with their fellow subclinical CNV eyes (10.823 ± 3.365%, = 0.115).

Conclusions: There is a notable prevalence of subclinical CNV in fellow eyes with unilateral exudative CNV, and significantly greater choriocapillaris nonperfusion adjacent to all CNV lesions. We identified a trend for increased choriocapillaris nonperfusion in exudative AMD eyes as compared with their fellow subclinical CNV eyes, which deserves further study.

Translational Relevance: OCTA can be useful in clinical practice to detect subclinical CNV and study choriocapillaris dysfunction.

Treppo, E., L. Quartuccio, G. Ragab, and S. De Vita, "Rheumatologic manifestations of Hepatitis C Virus.", Minerva Medica, 2020. Abstract
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Trescot, A., H. Hansen, S. Helm, G. Varrassi, and M. Iskander, "Pain Management Techniques and Practice: New Approaches, Modifications of Techniques, and Future Directions", Anesthesiology Research and Practice, vol. 2012, pp. 1, 2012. Abstract

The practice of pain medicine has radically changed over the last twenty years, morphing from an almost exclusively anesthesia-based, recovery room, and procedure-oriented part-time practice into a multidisciplinary, multimodality, multispecialty field. These changes have been the consequence and the stimuli for the expansion of new medications and techniques, which have improved the diagnosis and treatment of painful conditions. This issue attempts to highlight some of the advances in anesthesiology and pain, including epidural analgesia, spinal cord stimulation, and trigger point diagnosis and treatment. There is also a case report of a technique utilizing transforaminal blood patches to treat intracranial hypotension, analogous to postdural puncture headaches. Particularly intriguing, given the current controversy regarding the role of opioids in the management of chronic pain, is the report of the lasting developmental delays seen in infant rats exposed to fentanyl. This observation could have a significant impact on the decision to initiate opioids in human infants and children and adds data to the current dilemma.

Pain medicine is a rapidly growing field, and the innovations described in this issue move the field further into the future. Hopefully, the reader will be encouraged to utilize and expand on these topics in their own practice

Treuter, S., A. Schuh, W. H?nle, M. S. Ismail, T. N. Chirag, and A. Fujak., "Long-Term Results of Total Knee Arthroplasty Following High Tibial Osteotomy According to Wagner", International Orthopaedics, 2011. Abstract

Purpose: There is relatively little information available about the long-term results of total knee arthroplasty (TKA) following high tibial osteotomy. The aim of our study was to share our experiences and long-term results of TKA after a previous closing wedge high tibial osteotomy according to Wagner.

Treuter, S., A. Schuh, W. Hönle, M. S. Ismail, T. N. Chirag, and A. Fujak, "Long-term results of total knee arthroplasty following high tibial osteotomy according to {Wagner}", International Orthopaedics, vol. 36, no. 4, pp. 761–764, 2012. AbstractWebsite

PurposeThere is relatively little information available about the long-term results of total knee arthroplasty (TKA) following high tibial osteotomy. The aim of our study was to share our experiences and long-term results of TKA after a previous closing wedge high tibial osteotomy according to Wagner.MethodsIn a retrospective study we identified 48 consecutive patients who had undergone TKA after a previous closing wedge high tibial osteotomy according to Wagner with a follow-up of over ten years. The average duration of follow-up after the TKA was 13.3 years (min 10.0, max 15.5). X-rays were taken in two planes before TKA, one week after TKA and at the latest follow-up. Tibio-femoral alignment was measured on weightbearing long-leg anteroposterior radiographs. Radiolucent lines at the latest follow-up were documented. Functional evaluations were performed preoperatively and postoperatively (at the time of latest follow-up).ResultsThe mean Knee Society function score increased from 63.1 points preoperatively to 90.0 points postoperatively. The mean overall Knee Society score increased from 93.2 points preoperatively to 160.8 points postoperatively. The mean average femoro-tibial angle was corrected from varus 0.8° (varus 14°–valgus 8.0°) preoperatively to valgus 7.6° (valgus 2–9°) at the last follow-up.ConclusionsThe closing wedge high tibial osteotomy according to Wagner does not compromise subsequent total knee replacement and leads to good clinical and radiological results.

Treutter, D., D. Wang, M. A. Farag, G. D. Baires, and M. Neumüller., "Diversity of Phenolic Profiles in the Fruit Skin of Prunus domestica Plums and related species", J Agric Food Chem, vol. 60, issue 48, pp. 12011-12019. , 2012. farag_et_al._2012_journal_of_agric_food_chem.pdf
Trevisan, A., Amgad El-Deib, R. Gagnon, and J. Mahseredjian, "Generic EMT-type full- converter wind turbine model based on an externally excited gearless synchronous generator system for power systems studies", IEEE Transactions on Power Delivery, vol. 33, issue 6, pp. 2284-2293, 2018.
Tricoli, L., A. Naeem, E. Parasido, J. P. Mikhaiel, M. U. Choudhry, D. L. Berry, I. A. Abdelgawad, R. J. Lee, A. S. Feldman, C. Ihemelandu, et al., "Characterization of the effects of defined, multidimensional culture conditions on conditionally reprogrammed primary human prostate cells", Oncotarget, vol. 9, issue 2, pp. 2193–2207., 2018. oncotarget-09-2193.pdf
Trieb, F., J. Sattler, A. Anthrakidis, C. Faber, T. Fend, J. Göttsche, A. Khalil, and D. T. G. Wambeogo, Secondary Applications, , Submitted. Abstract
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Tripathi, S., and et al, "Bipronged inverted impacted third molar- a rarest of rare case report (Prof. Emad Daif was a peer reviewer for this article).", British Journal of Medicine and Medical Research, vol. 9, issue 9, pp. 1-5, 2015.
Trivedi, R. H., A. M. Izak, L. Werner, T. A. Macky, S. K. Pandey, and D. J. Apple, "Interlenticular opacification of piggyback intraocular lenses.", International ophthalmology clinics, vol. 41, issue 3, pp. 47-62, 2001 Summer.
Trivedi, R. H., L. Werner, D. J. Apple, A. M. Izak, S. K. Pandey, and T. A. Macky, "Viscoanesthesia. Part I: toxicity to corneal endothelial cells in a rabbit model.", Journal of cataract and refractive surgery, vol. 29, issue 3, pp. 550-5, 2003 Mar. Abstract

PURPOSE: To evaluate the toxicity of a solution combining sodium hyaluronate 1.5% with lidocaine (0.5%, 1.0%, or 1.65%) to the rabbit corneal endothelium.

SETTING: Center for Research on Ocular Therapeutics and Biodevices, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA.

METHODS: Each rabbit cornea was excised, and the endothelium was exposed to 1 of the following solutions for 20 minutes: viscoanesthetic solution (0.5%, 1.0%, or 1.65% lidocaine in sodium hyaluronate 1.5%; 5 corneas each), sodium hyaluronate 1.5% (n = 5), balanced salt solution (BSS(R)) (n = 5), mitomycin-C 0.02% (n = 2), dextran 15% (n = 2), or distilled water (n = 2). The endothelium was then stained with trypan blue and alizarin red. Two corneas were stained immediately after excision. Cell morphology and damage to the corneal endothelium were analyzed by microscopic examination.

RESULTS: The endothelium in the corneas of the viscoanesthetic groups was comparable to that in the sodium hyaluronate 1.5% and the BSS groups and to the corneas not exposed to any solution. In some areas of the 1.0% and the 1.65% viscoanesthesia groups, the corneal endothelial cells presented irregular intercellular borders. Staining with trypan blue, which indicates cellular damage, was observed in some linear areas corresponding to corneal folds in all groups. The folds were probably caused during manipulation for corneal excision and staining. The corneal endothelium was destroyed in the mitomycin group. In the dextran and distilled-water groups, morphological alterations probably resulting from osmotic changes were observed.

CONCLUSIONS: The 3 concentrations of viscoanesthetic solutions appeared to be safe to rabbit corneal endothelium.

Trojanowski, B. M., H. H. Salem, H. Neubauer, E. Simon, M. Wagner, R. Dorajoo, B. O. Boehm, L. Labriola, T. Wirth, and B. Baumann, "Elevated β-cell stress levels promote severe diabetes development in mice with MODY4", J Endocrinol, vol. 244, issue 2, pp. 323–337, 2020.
Troschel, F. M., A. Minte, Y. M. Ismail, A. Kamal, M. S. Abdullah, S. H. Ahmed, M. Deffner, B. Kemper, L. Kiesel, H. T. Eich, et al., " Knockdown of Musashi RNA Binding Proteins Decreases Radioresistance but Enhances Cell Motility and Invasion in Triple-Negative Breast Cancer ", International Journal of Molecular Sciences, vol. 21, issue 6, pp. 2169., 2020. international_journal_of_molecular_sciences.pdf
Trout, R., and B. R. using Biofloc, "JOURNAL HIGHLIGHTS", Visible Implant Tags for Batch and Individual ID, vol. 38, no. 11, pp. 521, 2013. Abstract
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Trout, J. M., and M. M. Mashaly, "Effects of in vitro corticosterone on chicken T‐and B‐lymphocyte proliferation", British poultry science, vol. 36, issue 5: Taylor & Francis, pp. 813-820, 1995. Abstract
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Trout, J. M., H. S. Siegel, and M. M. Mashaly, "CHANGES IN THE PROFILE OF CIRCULATING WHITE BLOOD-CELLS FOLLOWING ANTIGEN CHALLENGE IN IMMATURE MALE CHICKENS", FEDERATION PROCEEDINGS, vol. 46, issue 3: FEDERATION AMER SOC EXP BIOL 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998, pp. 529-529, 1987. Abstract
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Trout, J. M., M. M. Mashaly, and H. S. Siegel, "Changes in blood and spleen lymphocyte populations following antigen challenge in immature male chickens", British poultry science, vol. 37, issue 4: Taylor & Francis, pp. 819-827, 1996. Abstract
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Trout, J. M., M. A. G. D. I. M. MASHALY, and H. S. Siegel, "Changes in the profiles of circulating white blood cells, corticosterone, T< sub> 3 and T< sub> 4 during the initiation of humoral immunity in immature male chickens", Developmental & Comparative Immunology, vol. 12, issue 2: Elsevier, pp. 331-346, 1988. Abstract
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Trout, R., and B. R. using Biofloc, "JOURNAL HIGHLIGHTS", Visible Implant Tags for Batch and Individual ID, vol. 38, no. 11, pp. 521, 2013. Abstract
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