Audiological and Surgical Correlates of Myringoplasty Associated with Ethnography in the Bay of Plenty, New Zealand.

INTRODUCTION: This retrospective cohort study of myringoplasty performed at Tauranga Hospital, Bay of Plenty, New Zealand from 2010 to 2020 sought to identify predictive factors for successful myringoplasty with particular consideration given to the known high prevalence of middle ear conditions in New Zealand Maori. METHODS: Outcomes were surgical success (perforation closure at 1 month) and hearing improvement, which were correlated against demographic, pathological, and surgical variables. RESULTS: 174 patients underwent 221 procedures (139 in children under 18 years old), with 66.1% of patients being New Zealand Maori and 24.7% New Zealand European ethnicity. Normalized by population demographics, New Zealand Maori were 2.3 times overrepresented, whereas New Zealand Europeans were underrepresented by 0.34 times (a 6.8 times relative treatment differential). The rate of surgical success was 84.6%, independent of patient age, gender, and ethnicity. A postauricular approach and the use of temporalis fascia grafts were both correlated with optimal success rates, whereas early postoperative infection (<1 month) was correlated with ∼3 times increased failure. Myringoplasty improved hearing in 83.1% of patients (average air-bone gap reduction of 10.7 dB). New Zealand Maori patients had ∼4 times greater preoperative conductive hearing loss compared to New Zealand Europeans, but benefited the most from myringoplasty. DISCUSSION/CONCLUSION: New Zealand Maori and pediatric populations required greater access to myringoplasty, achieving good surgical and audiological outcomes. Myringoplasty is highly effective and significantly improves hearing, particularly for New Zealand Maori. Pediatric success rates were equivalent to adults, supporting timely myringoplasty to minimize morbidity from untreated perforations.

Clinical utility of local over general anesthetic tonsillectomy using the BiZact™ device.

PURPOSE: Tonsillectomy under general anesthesia may be viewed preferentially to local anesthesia, due to mitigation of potential airway compromise secondary to intraoperative hemorrhage, patient discomfort and anxiety. However, this is offset by risk of increased trauma (via the endotracheal tube and gag), adverse medication reactions and cost. Here we evaluated the case for use of local anesthesia in tonsillectomy using the BiZact™ (Medtronic) device by comparing surgical outcomes and cost factors across patients where either local or general anesthesia was employed. MATERIALS AND METHODS: Retrospective cohort study of 59 BiZact™ tonsillectomy patients (38 under local anesthetic, and 21 under general anesthetic) from a single surgeon at Tauranga Hospital (public) and Grace Hospital (private) in New Zealand; March 2018 to June 2021. RESULTS: Neither patient group had any primary postoperative hemorrhage and there was comparable incidence of secondary hemorrhage (one case in each cohort). Local anesthetic tonsillectomy was well tolerated with only 2 patients requiring conversion to general anesthetic secondary to anxiety. Local anesthetic proved to be cost-effective, with a halving of hospital length of stay and significant associated overall cost saving, and did not add significantly to operating or total theatre time. Local anesthetic tonsillectomies where perioperative sedation was not required were associated with additional reductions in recovery and overall hospital stay, and cost. CONCLUSIONS: Local anesthetic BiZact™ tonsillectomy is evidently safe and cost-effective.

Gene Electrotransfer via Conductivity-Clamped Electric Field Focusing Pivots Sensori-Motor DNA Therapeutics: "A Spoonful of Sugar Helps the Medicine Go Down".

Viral vectors and lipofection-based gene therapies have dispersion-dependent transduction/transfection profiles that thwart precise targeting. The study describes the development of focused close-field gene electrotransfer (GET) technology, refining spatial control of gene expression. Integration of fluidics for precise delivery of "naked" plasmid deoxyribonucleic acid (DNA) in sucrose carrier within the focused electric field enables negative biasing of near-field conductivity ("conductivity-clamping"-CC), increasing the efficiency of plasma membrane molecular translocation. This enables titratable gene delivery with unprecedently low charge transfer. The clinic-ready bionics-derived CC-GET device achieved neurotrophin-encoding miniplasmid DNA delivery to the cochlea to promote auditory nerve regeneration; validated in deafened guinea pig and cat models, leading to improved central auditory tuning with bionics-based hearing. The performance of CC-GET is evaluated in the brain, an organ problematic for pulsed electric field-based plasmid DNA delivery, due to high required currents causing Joule-heating and damaging electroporation. Here CC-GET enables safe precision targeting of gene expression. In the guinea pig, reporter expression is enabled in physiologically critical brainstem regions, and in the striatum (globus pallidus region) delivery of a red-shifted channelrhodopsin and a genetically-encoded Ca2+ sensor, achieved photoactivated neuromodulation relevant to the treatment of Parkinson's Disease and other focal brain disorders.

Australian Scorpion Hormurus waigiensis Venom Fractions Show Broad Bioactivity Through Modulation of Bio-Impedance and Cytosolic Calcium.

Scorpion venoms are a rich source of bioactive molecules, but characterisation of toxin peptides affecting cytosolic Ca2+, central to cell signalling and cell death, is limited. We undertook a functional screening of the venom of the Australian scorpion Hormurus waigiensis to determine the breadth of Ca2+ mobilisation. A human embryonic kidney (HEK293) cell line stably expressing the genetically encoded Ca2+ reporter GCaMP5G and the rabbit type 1 ryanodine receptor (RyR1) was developed as a biosensor. Size-exclusion Fast Protein Liquid Chromatography separated the venom into 53 fractions, constituting 12 chromatographic peaks. Liquid chromatography mass spectroscopy identified 182 distinct molecules with 3 to 63 components per peak. The molecular weights varied from 258 Da-13.6 kDa, with 53% under 1 kDa. The majority of the venom chromatographic peaks (tested as six venom pools) were found to reversibly modulate cell monolayer bioimpedance, detected using the xCELLigence platform (ACEA Biosciences). Confocal Ca2+ imaging showed 9/14 peak samples, with molecules spanning the molecular size range, increased cytosolic Ca2+ mobilization. H. waigiensis venom Ca2+ activity was correlated with changes in bio-impedance, reflecting multi-modal toxin actions on cell physiology across the venom proteome.

Scorpion toxin peptide action at the ion channel subunit level.

This review categorizes functionally validated actions of defined scorpion toxin (SCTX) neuropeptides across ion channel subclasses, highlighting key trends in this rapidly evolving field. Scorpion envenomation is a common event in many tropical and subtropical countries, with neuropharmacological actions, particularly autonomic nervous system modulation, causing significant mortality. The primary active agents within scorpion venoms are a diverse group of small neuropeptides that elicit specific potent actions across a wide range of ion channel classes. The identification and functional characterisation of these SCTX peptides has tremendous potential for development of novel pharmaceuticals that advance knowledge of ion channels and establish lead compounds for treatment of excitable tissue disorders. This review delineates the unique specificities of 320 individual SCTX peptides that collectively act on 41 ion channel subclasses. Thus the SCTX research field has significant translational implications for pathophysiology spanning neurotransmission, neurohumoral signalling, sensori-motor systems and excitation-contraction coupling. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.'