Selective CNS Targeting and Distribution with a Refined Region-Specific Intranasal Delivery Technique via the Olfactory Mucosa

Intranasal drug delivery is a promising approach for the delivery of drugs to the CNS, but too heterogenous, unprecise delivery methods without standardization decrease the quality of many studies in rodents. Thus, the lack of a precise and region-specific application technique for mice is a major drawback. In this study, a previously developed catheter-based refined technique was validated against the conventional pipette-based method and used to specifically reach the olfactory or the respiratory nasal regions. This study successfully demonstrated region-specific administration at the olfactory mucosa resulting in over 20% of the administered fluorescein dose in the olfactory bulbs, and no peripheral bioactivity of insulin detemir and Fc-dependent uptake of two murine IgG1 (11C7 and P3X) along the olfactory pathway to cortex and hippocampus. An scFv of 11C7 showed hardly any uptake to the CNS. Elimination was dependent on the presence of the IgG’s antigen. In summary, it was successfully demonstrated that region-specific intranasal administration via the olfactory region resulted in improved brain targeting and reduced peripheral targeting in mice. The data are discussed with regard to their clinical potential.

High Time Resolution Measurements of Droplet Evaporation Kinetics and Particle Crystallisation

A refined technique for observing the complete evaporation behaviour of free-falling droplets, from droplet generation to complete solvent evaporation, with ultra-high time resolution is introduced and benchmarked. High-resolution phase-delay stroboscopic...

Skin swabbing is a refined technique to collect DNA from model fish species

Model fish species such as sticklebacks and zebrafish are frequently used in studies that require DNA to be collected from live animals. This is typically achieved by fin clipping, a procedure that is simple and reliable to perform but that can harm fish. An alternative procedure to sample DNA involves swabbing the skin to collect mucus and epithelial cells. Although swabbing appears to be less invasive than fin clipping, it still requires fish to be netted, held in air and handled—procedures that can cause stress. In this study we combine behavioural and physiological analyses to investigate changes in gene expression, behaviour and welfare after fin clipping and swabbing. Swabbing led to a smaller change in cortisol release and behaviour on the first day of analysis compared to fin clipping. It also led to less variability in data suggesting that fewer animals need to be measured after using this technique. However, swabbing triggered some longer term changes in zebrafish behaviour suggesting a delayed response to sample collection. Skin swabbing does not require the use of anaesthetics and triggers fewer changes in behaviour and physiology than fin clipping. It is therefore a more refined technique for DNA collection with the potential to improve fish health and welfare.

Nuances of the Direct Brow Lift: Oculoplastic Surgeons’ Perspective

The direct supraciliary brow lift is an effective procedure to treat brow ptosis, limited by risk of a cosmetically undesirable scar. We performed a comprehensive literature review of direct supraciliary brow lift techniques and provide a summary of the key considerations. The optimal direct brow lift is initiated with thoughtful incision design and a carefully beveled supraciliary incision. Subcutaneous tissue debulking and wound edge undermining optimize wound eversion and approximation. A layered meticulously executed skin closure is essential for optimal cosmesis. The senior author’s personal technique, incorporating these concepts, is described and illustrated. We reviewed 76 patients (141 brows) who underwent our refined technique. At the time of final follow-up visit (average 4.9 months), 72 patients (94.7%) reported complete satisfaction with results. Adverse outcomes were found in 4 patients (5.3%) and included transient paresthesias (n = 3) and hypertrophic scarring (n = 1). Postoperative care routinely included the use of topical steroids and additional treatment with microneedling and 5-fluorouracil in 2 patients (2.6%) to optimize healing. The direct supraciliary brow lift is a minimally invasive and effective procedure to correct brow ptosis and may yield excellent cosmesis when key principles are utilized.

OLIVER KNUSSEN (1952–2018)Four Late Poems and an Epigram of Rainer Maria Rilke (1988)

This chapter examines a compelling solo work by Oliver Knussen in which his command of style and acute sensitivity to vocal and verbal subtleties are immediately apparent. Here, pitches and rhythms are calibrated with precision, and a host of detailed dynamic and expressive markings guide the performer to a disciplined and faithful reading. Though fragmentary in appearance, and larded with meticulous shadings and accents, the music flows in long paragraphs, and its subtle intricacies result in a sense of spontaneous rhythmic freedom, almost as if improvised. The agile vocal lines moreover teem with shifting emotions, and shows a refined technique to advantage.

Influence of Pile Geometry on Responses of End-Bearing Pile Groups Subjected to Vertical Dynamic Loads

An analytical solution is presented for evaluating the dynamic responses of pile groups subjected to vertical harmonic loads. The solution allows us to consider the effects of pile geometry on the pile head impedance of the vertically loaded pile groups by the use of a new dynamic interaction factor. To this end, the stress distributions of the soil surrounding the vertically vibrating pile is first determined for calculating the pile–pile interaction factor, instead of the classical interaction factor based on two-pile displacements in past studies. Accordingly, the impedances of the pile group are derived using the proposed pile–pile interaction factor and the superposition principle. Some selected examples are presented to demonstrate the proposed refined technique for evaluating the dynamic characteristics of the pile group.

Refined Approach to Preservation of the Inferior Alveolar Nerve during Resection and Primary Reconstruction of the Mandible

Sacrifice of the inferior alveolar nerve (IAN) during resection of the mandible is taken as a rule. In 1987, Jensen and Nock described a technique that permitted placement of dental implants in the atrophied mandibular alveolar ridge that lacked sufficient vertical height superior to the mandibular canal. This technique was used by some authors to preserve continuity of the IAN during resection of the mandible in patients with benign tumors. The described techniques are traumatic, time-consuming, and not precise. We propose a new refined technique of preservation of IAN with use of a guide to approach mandibular canal, cutting guides with a slot for a relocated IAN, and a new approach to positioning of the fixating screws. We assessed the effectiveness of this new technique with use of an electro-odontometer. In 21 cases, we demonstrated a refined approach to preservation of the IAN. In 7 patients (33%), the IAN was preserved on one side and in 14 patients (67%), on both sides. Sensation in the lower lip was restored in 18 patients (86%). These patients generally recovered sensation within 22 days postoperatively. This proposed technique makes preservation of IAN easier, faster, less traumatic, and more predictable. In this article, we describe criteria for the patients with cancer of oral mucosa to be admitted for this procedure. Restored sensation in the lower lip of the patients who have undergone resection of the mandible significantly improves their quality of life.