This study examined the effects of a combination corticosteroid plus long-acting beta2 -adrenergic agonist inhaler (IC) on rabbit phonation.
White New Zealand male rabbits were assigned randomly to experimental and control groups (n = 11 per group). The experimental group received twice-daily doses of Advair HFA™ (fluticasone propionate 45 mcg and salmeterol 21 mcg) via a veterinary facemask with 1-way valve and spacer; the control group received aerosolized saline. After 8 weeks, animals were euthanized, larynges excised, frozen, and subsequently thawed and mounted on a standard bench apparatus. Phonation was elicited during 15 successive trials, and phonation threshold pressure (PTP; cmH2 O) and flow (PTF; L/min) were quantified.
Repeated measures analysis of variance indicated significant differences between the experimental and control groups (p < 0.05). Mean PTP and PTF values were higher (worse) for rabbits that received Advair HFA™.
Following 8-week exposure to ICs, rabbit larynges required greater air pressure and flow to initiate phonation. Because even modest phonation onset differences can have a meaningful clinical impact on voice function, these findings suggest that LABA ICs may put patients at risk for voice disorders. Furthermore, these voice disorders may occur within a relatively short timeframe. The results from this study have important clinical implications for voice care in those who use ICs.
NA Laryngoscope, 133:2680-2686, 2023.

BACKGROUND: This study aims to compare preclinical visual-quality metrics and halo size of intraocular lenses (IOL) with enhanced intermediate vision to a standard monofocal lens.
METHODS: Three monofocal- IOL models with an extended-depth-of-focus (EDoF) intended for monocular implantation (Tecnis ICB00, AE2UV/ZOE, and IsoPure) and one for monovision (RayOne EMV) were compared against a standard monofocal lens (Tecnis ZCB00). An optical-metrology station was used in the assessment of IOLs\' optical quality in polychromatic light. The imaging quality was compared with metrics derived from the optical transfer function. Halo size was estimated from the projection of the point spread function under scotopic pupil.
RESULTS: The monofocal IOL showed the highest image quality at the far focus. The ICB00\'s, the AE2UV/ZOE\'s, and the IsoPure\'s performance at - 1D was superior to that of the monofocal lens. The monocular defocus tolerance of the RayOne EMV was comparable with that of the ZCB00. The RayOne EMV\'s intermediate range was improved in a monovision configuration (- 1D offset). This approach, however, yielded the largest halo area, i.e., 53% of the ZCB00\'s halo, compared to 34% for the IsoPure, 14% for the AE2UV/ZOE, and 8% for the ICB00.
CONCLUSIONS: The mono-EDoF models have a clear advantage over the standard monofocal lens by expanded imaging capability beyond - 0.5D. Although the RayOne EMV provided the largest (binocular) visual-range extension, it was at the expense of monocular vision and higher susceptibility to halo. The ICB00\'s and the AE2UV/ZOE\'s halo-profile was similar to that of the ZCB00, indicating their low potential to induce photic phenomena.

BACKGROUND: The diagnostic work-up to reveal etiology in a young ischemic stroke (IS) patient includes evaluation for high-risk source of cardioembolism (HRCE), since this subtype associates with high early recurrence rate and mortality. We investigated the association of ECG findings with a final etiologic subgroup of HRCE in a cohort of young patients with first-ever IS.
METHODS: The Helsinki Young Stroke Registry includes IS patients aged 15 to 49 years admitted between 1994 and 2007. Blinded to other clinical data, we analyzed a 12-lead resting ECG obtained 1-14 days after the onset of stroke symptoms in 690 patients. We then compared the ECG findings between a final diagnosis of HRCE (n=78) and other/undetermined causes (n=612). We used multivariate logistic regression to study the association between ECG parameters and HRCE.
RESULTS: Of our cohort (63% male), 35% showed ECG abnormality, the most common being T-wave inversion (16%), left ventricular hypertrophy (14%), prolonged P-wave (13%), and prolonged QTc (12%). 3% had atrial fibrillation (AF), and 4% P-terminal force (PTF). Of the continuous parameters, longer QRS-duration, QTc, and wider QRS-T-angle independently associated with HRCE. After AF, PTF had the strongest independent association with HRCE (odds ratio=44.32, 95% confidence interval=[10.51-186.83]), followed by a QRS-T angle >110° (8.29 [3.55-19.32]), T-wave inversion (5.06, 2.54-10.05), and prolonged QTc (3.02 [1.39-6.56]).
CONCLUSIONS: Routine ECG provides useful information for directing the work-up of a young IS patient. In addition to AF, PTF in particular showed a strong association with etiology of HRCE.

Human RNA polymerase III transcribes small untranslated RNAs that contribute to the regulation of essential cellular processes, including transcription, RNA processing and translation. Analysis of this transcription system by in vitro transcription techniques has largely contributed to the discovery of its transcription factors and to the understanding of the regulation of human RNA polymerase III transcription. Here we review some of the key steps that led to the identification of transcription factors and to the definition of minimal promoter sequences for human RNA polymerase III transcription.

BACKGROUND: The preclinical efficacy and safety of rVIII-SingleChain (CSL627), a novel recombinant single-chain factor VIII, was assessed in a series of animal studies.
METHODS: In the tail-clip bleeding model, hemophilia A mice were injected with escalating doses (1-150 IU/kg) of rVIII-SingleChain, B-domain deleted (BDD) rFVIII (ReFacto AF(®)), or full-length rFVIII products (Advate(®), Helixate(®)). Total blood loss and the percentage of animals in which hemostasis occurred were assessed in this observer-blinded, randomized study. In a second non-randomized study in hemophilia A mice, thromboelastographic analysis, thrombin generation, and activated partial thromboplastin time assays were performed. General safety and toxicity were assessed in three animal species, including determination of the prothrombotic potential of rVIII-SingleChain in a rabbit venous thrombosis model.
RESULTS: Under acute bleeding conditions, the effect of rVIII-SingleChain on total blood loss and hemostasis was indistinguishable from BDD and full-length rFVIII. rVIII-SingleChain and full-length rFVIII (both 20 IU/kg) corrected thromboelastographic parameters, activated partial thromboplastin time, and thrombin generation to a similar degree in hemophilia A mice. In a thrombosis model, the effect of rVIII-SingleChain on thrombus incidence was non-significant and comparable to BDD rFVIII at doses up to 500 IU/kg. Treatment with rVIII-SingleChain did not cause anaphylactic reaction or local intolerance in safety and toxicity studies, and demonstrated an excellent overall safety profile.
CONCLUSIONS: rVIII-SingleChain showed convincing hemostatic efficacy and excellent tolerability in animal studies, warranting continued investigation in human Phase I/III trials (AFFINITY).