Orthognathic Surgery Rates in Furlow Double-Opposing Z-Plasty Versus Straight-Line Repair: A Review of Three Decades of Experience.

OBJECTIVE: The influence of different surgical techniques on maxillary growth remains unclear. This study investigates the long-term impact of Furlow double-opposing Z-plasty versus straight-line repair (SLR) techniques on midface growth and subsequent orthognathic surgery. DESIGN: Retrospective cohort study. SETTING: Tertiary children's hospital. PATIENTS/PARTICIPANTS: This study evaluated patients who underwent primary palatoplasty with Furlow or SLR techniques from 1994-2023. Patients were >14 years old at their most recent follow-up. INTERVENTIONS: No interventions were performed. MAIN OUTCOME MEASURE(S): Primary outcomes were orthognathic surgery and orthognathic surgery recommendation rates to correct midface hypoplasia (MFH). Cephalometrics at the time of orthognathic surgery recommendation were traced to validate MFH. RESULTS: In total, 1857 patients underwent palatoplasty, of which 335 met inclusion criteria (49 SLR, 286 Furlow). Average age at last follow-up was 18.5±2.6 years. Patients who underwent Furlow versus SLR showed no significant difference in orthognathic surgery rates (p=0.428) or recommendation for orthognathic surgery rates (p=0.900). Patients recommended to undergo orthognathic surgery had more negative ANB angles (p<0.001) and smaller SNA angles (p<0.001) than patients not recommended for orthognathic surgery, demonstrating maxillary hypoplasia. Upon multivariate regression, patients with Veau III and IV clefts had an increased need for orthognathic surgery, p=0.047 and p=0.008, respectively. CONCLUSIONS: Our findings suggest that higher cleft severity contributes to future orthognathic surgery. However, palatoplasty technique did not influence orthognathic surgery rates. Our results provide valuable data when surgeons are considering the impact of palatoplasty technique on sagittal growth restriction.

Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer's disease.

Reduction of amyloid beta (Aß) has been shown to be effective in treating Alzheimer's disease (AD), but the underlying assumption that neurons are the main source of pathogenic Aß is untested. Here, we challenge this prevailing belief by demonstrating that oligodendrocytes are an important source of Aß in the human brain and play a key role in promoting abnormal neuronal hyperactivity in an AD knock-in mouse model. We show that selectively suppressing oligodendrocyte Aß production improves AD brain pathology and restores neuronal function in the mouse model in vivo. Our findings suggest that targeting oligodendrocyte Aß production could be a promising therapeutic strategy for treating AD.

Differences in cancer clinical trial activity and trial characteristics at metropolitan and rural trial sites in Victoria, Australia.

OBJECTIVE: Cancer clinical trials (CCTs) provide access to emerging therapies and extra clinical care. We aimed to describe the volume and characteristics of CCTs available across Victoria, Australia, and identify factors associated with rural trial location. METHODS: Quantitative analysis of secondary data from Cancer Council Victoria's Clinical Trials Management Scheme dataset. DESIGN: A cross-sectional study design was used. SETTING: CCTs were available Victoria-wide in 2018. PARTICIPANTS: There were 1669 CCTs and 5909 CCT participants. MAIN OUTCOME MEASURES: Rural CCT location was assessed as a binary variable with categories of 'yes' (modified Monash [MM] categories 2-7) and 'no' (MM category 1). MM categories were determined from postcodes. The highest ('least rural') MM category was used for postcodes with multiple MM categories. RESULTS: Of 1669 CCTs, 168 (10.1%) were conducted in rural areas. Of 5909 CCT participants, 315 (5.3%) participated in rural CCTs. There were 526 CCTs (31.5%) with 1907 (32.3%) newly enrolled participants. Of 1892 newly enrolled participants with postcode data, 488 (25.8%) were rural residents. Of them, 368 (75.4%) participated in metropolitan CCTs. In a multivariable logistic regression analysis for all 1669 CCTs, odds of a rural rather than metropolitan CCT location were significantly (p-value <0.05) lower for early-phase than late-phase trials and non-solid than solid tumour trials but significantly (p-value <0.05) higher for non-industry than industry-sponsored trials. CONCLUSIONS: In Victoria, 10% of CCTs are at rural sites. Most rural-residing CCT participants travel to metropolitan sites, where there are more late-phase, non-solid-tumour and industry-sponsored trials. Approaches to increase the volume and variety of rural CCTs should be considered.

Controlling Excited State Localization in Bichromophoric Photosensitizers via the Bridging Group.

A series of photosensitizers comprised of both an inorganic and an organic chromophore are investigated in a joint synthetic, spectroscopic, and theoretical study. This bichromophoric design strategy provides a means by which to significantly increase the excited state lifetime by isolating the excited state away from the metal center following intersystem crossing. A variable bridging group is incorporated between the donor and acceptor units of the organic chromophore, and its influence on the excited state properties is explored. The Franck-Condon (FC) photophysics and subsequent excited state relaxation pathways are investigated with a suite of steady-state and time-resolved spectroscopic techniques in combination with scalar-relativistic quantum chemical calculations. It is demonstrated that the presence of an electronically conducting bridge that facilitates donor-acceptor communication is vital to generate long-lived (32 to 45 µs), charge-separated states with organic character. In contrast, when an insulating 1,2,3-triazole bridge is used, the excited state properties are dominated by the inorganic chromophore, with a notably shorter lifetime of 60 ns. This method of extending the lifetime of a molecular photosensitizer is, therefore, of interest for a range of molecular electronic devices and photophysical applications.

PolyGR and polyPR knock-in mice reveal a conserved neuroprotective extracellular matrix signature in C9orf72 ALS/FTD neurons.

Dipeptide repeat proteins are a major pathogenic feature of C9orf72 amyotrophic lateral sclerosis (C9ALS)/frontotemporal dementia (FTD) pathology, but their physiological impact has yet to be fully determined. Here we generated C9orf72 dipeptide repeat knock-in mouse models characterized by expression of 400 codon-optimized polyGR or polyPR repeats, and heterozygous C9orf72 reduction. (GR)400 and (PR)400 knock-in mice recapitulate key features of C9ALS/FTD, including cortical neuronal hyperexcitability, age-dependent spinal motor neuron loss and progressive motor dysfunction. Quantitative proteomics revealed an increase in extracellular matrix (ECM) proteins in (GR)400 and (PR)400 spinal cord, with the collagen COL6A1 the most increased protein. TGF-ß1 was one of the top predicted regulators of this ECM signature and polyGR expression in human induced pluripotent stem cell neurons was sufficient to induce TGF-ß1 followed by COL6A1. Knockdown of TGF-ß1 or COL6A1 orthologues in polyGR model Drosophila exacerbated neurodegeneration, while expression of TGF-ß1 or COL6A1 in induced pluripotent stem cell-derived motor neurons of patients with C9ALS/FTD protected against glutamate-induced cell death. Altogether, our findings reveal a neuroprotective and conserved ECM signature in C9ALS/FTD.

Twelve tips for designing and implementing peer-led assessment writing schemes in health professions education.

Peer-led assessment (PLA) has gained increasing prominence within health professions education as an effective means of engaging learners in the process of assessment writing and practice. Involving students in various stages of the assessment lifecycle, including item writing, quality assurance, and feedback, not only facilitates the creation of high-quality item banks with minimal faculty input but also promotes the development of students' assessment literacy and fosters their growth as teachers. The advantages of involving students in the generation of assessments are evident from a pedagogical standpoint, benefiting both students and faculty. However, faculty members may face uncertainty when it comes to implementing such approaches effectively. To address this concern, this paper presents twelve tips that offer guidance on important considerations for the successful implementation of peer-led assessment schemes in the context of health professions education.

Immune checkpoint inhibitor therapy for advanced cutaneous squamous cell carcinoma in Australia: a retrospective real world cohort study.

OBJECTIVES: To review the outcomes of immune checkpoint inhibitor (ICI) treatment of advanced cutaneous squamous cell carcinoma (CSCC) outside clinical trials. STUDY DESIGN: Retrospective observational study; review of patient records in fifteen Australian institutions. SETTING, PARTICIPANTS: All Australian adults with locally advanced or metastatic CSCC not amenable to curative surgery or radiotherapy treated with ICIs, 5 May 2017 - 23 May 2022, through a cemiplimab compassionate access scheme (Therapeutic Goods Administration Special Access Scheme) or who personally covered the cost of pembrolizumab prior to the start of the access scheme. MAIN OUTCOME MEASURES: Best overall response rate (ORR) according to standardised assessment criteria using the hierarchy: Response Evaluation Criteria in Solid Tumors (RECIST 1.1), the modified World Health Organization clinical response criteria, and the Positron Emission Tomography Response Criteria (PERCIST 1.0); overall and progression-free survival. RESULTS: A total of 286 people with advanced CSCC received ICI therapy during May 2017 - May 2022 (cemiplimab, 270; pembrolizumab, 16). Their median age was 75.2 years (range, 39.3-97.5 years) and 232 were men (81%); median follow-up time was 12.2 months (interquartile range, 5.5-20.5 months). Eighty-eight people (31%) were immunocompromised, 27 had autoimmune disease, and 59 of 277 (21%) had ECOG performance scores of 2 or 3. The ORR was 60% (166 of 278 evaluable patients): complete responses were recorded for 74 (27%) and partial responses for 92 patients (33%). Twelve-month overall survival was 78% (95% confidence interval [CI], 72-83%); progression-free survival was 65% (95% CI, 58-70%). Poorer ECOG performance status was associated with poorer overall survival (per unit: adjusted hazard ratio [aHR], 3.0; 95% CI, 2.0-4.3) and progression-free survival (aHR, 2.4; 95% CI, 1.8-3.3), as was being immunocompromised (overall: aHR, 1.8; 95% CI, 1.1-3.0; progression-free: aHR, 1.8; 95% CI, 1.2-2.7). Fifty-five people (19%) reported immune-related adverse events of grade 2 or higher; there were no treatment-related deaths. CONCLUSION: In our retrospective study, the effectiveness and toxicity of ICI therapy were similar to those determined in clinical trials. Our findings suggest that ICIs could be effective and well tolerated by people with advanced CSCC who are ineligible for clinical trials.

Esophageal Stent Migration Diagnosed With Point-of-Care Ultrasound.

This unique case depicts the first published report of a physician using point-of-care ultrasound to diagnose an esophageal stent migration. Discussed in this article are the sonographic findings that clinicians should be familiar with when evaluating patients with abdominal pain or chest pain who have a history of an esophageal stent. When coupled with a high index of suspicion, ultrasound can be one of the most portable, readily available, low-cost, and minimally invasive techniques for making a rapid diagnosis of esophageal stent migration.

Spontaneous intercostal herniation of lung and pleural fluid.

Thoracic hernias are characterized by the protrusion of the thoracic contents outside their normal anatomical confines. This case involves a left pleural effusion secondary to a spontaneous lung intercostal hernia (SLIH) in a 52-year-old male. Imaging revealed herniated pleural fluid in the intercostal space. Intra-operatively, there was herniation of the lung parenchyma into an intercostal defect. Pleural effusion secondary to a SLIH is an indication for surgical repair.

Dyskeratosis Congenita: A Case Report of a Patient With Coronary Artery Disease.

Clinical evidence demonstrates that patients with telomere biology disorders, such as dyskeratosis congenita, are more prone to coronary artery disease. We present the case of a 43-year-old female diagnosed with dyskeratosis congenita with critical cardiovascular disease. She underwent coronary artery bypass graft (CABG) with improvement of her cardiac function. Although this is a rare genetic disease, further studies are warranted to investigate the underlying pathophysiology of cardiovascular disease in patients with dyskeratosis congenita.