Maintenance of head and neck tumor on-chip: gateway to personalized treatment?

Aim: Head and neck squamous cell carcinomas (HNSCC) are solid tumors with low overall survival (40–60%). In a move toward personalized medicine, maintenance of tumor biopsies in microfluidic tissue culture devices is being developed. Methodology/ results: HNSCC (n = 15) was dissected (5–10 mg) and either analyzed immediately or cultured in a microfluidic device (37°C) for 48 h. No difference was observed in morphology between pre- and postculture specimens. Dissociated samples were analyzed using trypan blue exclusion (viability), propidium iodide flow cytometry (death) and MTS assay (proliferation) with no significant difference observed highlighting tissue maintenance. Computational fluid dynamics showed laminar flow within the system. Conclusion: The microfluidic culture system successfully maintained HNSCC for 48 h, the culture system will allow testing of different treatment modalities with response monitoring. Lay abstract: Head and neck cancers often have a poor treatment outcome. In order to study the response of the tissue, a miniaturized culture system has been developed to keep a small piece of tumor alive. In the current study, we show that small pieces of cancer tissue can be maintained in the system, using tissue structure and viability of single cells as a guide. In future work, patient equivalent treatments can be applied to these microculture systems to investigate individual patient tumor responses, which could help to guide treatment selection

Auditory Function in the Tc1 Mouse Model of Down Syndrome Suggests a Limited Region of Human Chromosome 21 Involved in Otitis Media

Down syndrome is one of the most common congenital disorders leading to a wide range of health problems in humans, including frequent otitis media. The Tc1 mouse carries a significant part of human chromosome 21 (Hsa21) in addition to the full set of mouse chromosomes and shares many phenotypes observed in humans affected by Down syndrome with trisomy of chromosome 21. However, it is unknown whether Tc1 mice exhibit a hearing phenotype and might thus represent a good model for understanding the hearing loss that is common in Down syndrome. In this study we carried out a structural and functional assessment of hearing in Tc1 mice. Auditory brainstem response (ABR) measurements in Tc1 mice showed normal thresholds compared to littermate controls and ABR waveform latencies and amplitudes were equivalent to controls. The gross anatomy of the middle and inner ears was also similar between Tc1 and control mice. The physiological properties of cochlear sensory receptors (inner and outer hair cells: IHCs and OHCs) were investigated using single-cell patch clamp recordings from the acutely dissected cochleae. Adult Tc1 IHCs exhibited normal resting membrane potentials and expressed all K+ currents characteristic of control hair cells. However, the size of the large conductance (BK) Ca2+ activated K+ current (IK,f), which enables rapid voltage responses essential for accurate sound encoding, was increased in Tc1 IHCs. All physiological properties investigated in OHCs were indistinguishable between the two genotypes. The normal functional hearing and the gross structural anatomy of the middle and inner ears in the Tc1 mouse contrast to that observed in the Ts65Dn model of Down syndrome which shows otitis media. Genes that are trisomic in Ts65Dn but disomic in Tc1 may predispose to otitis media when an additional copy is active

Timescales of Quartz Crystallization and the Longevity of the Bishop Giant Magma Body

Supereruptions violently transfer huge amounts (100 s–1000 s km3) of magma to the surface in a matter of days and testify to the existence of giant pools of magma at depth. The longevity of these giant magma bodies is of significant scientific and societal interest. Radiometric data on whole rocks, glasses, feldspar and zircon crystals have been used to suggest that the Bishop Tuff giant magma body, which erupted ∼760,000 years ago and created the Long Valley caldera (California), was long-lived (>100,000 years) and evolved rather slowly. In this work, we present four lines of evidence to constrain the timescales of crystallization of the Bishop magma body: (1) quartz residence times based on diffusional relaxation of Ti profiles, (2) quartz residence times based on the kinetics of faceting of melt inclusions, (3) quartz and feldspar crystallization times derived using quartz+feldspar crystal size distributions, and (4) timescales of cooling and crystallization based on thermodynamic and heat flow modeling. All of our estimates suggest quartz crystallization on timescales of <10,000 years, more typically within 500–3,000 years before eruption. We conclude that large-volume, crystal-poor magma bodies are ephemeral features that, once established, evolve on millennial timescales. We also suggest that zircon crystals, rather than recording the timescales of crystallization of a large pool of crystal-poor magma, record the extended periods of time necessary for maturation of the crust and establishment of these giant magma bodies

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe

Variation in postoperative outcomes of patients with intracranial tumors: insights from a prospective international cohort study during the COVID-19 pandemic

Background: This study assessed the international variation in surgical neuro-oncology practice and 30-day outcomes of patients who had surgery for an intracranial tumor during the COVID-19 pandemic. Methods: We prospectively included adults aged ≥18 years who underwent surgery for a malignant or benign intracranial tumor across 55 international hospitals from 26 countries. Each participating hospital recorded cases for 3 consecutive months from the start of the pandemic. We categorized patients’ location by World Bank income groups (high [HIC], upper-middle [UMIC], and low- and lower-middle [LLMIC]). Main outcomes were a change from routine management, SARS-CoV-2 infection, and 30-day mortality. We used a Bayesian multilevel logistic regression stratified by hospitals and adjusted for key confounders to estimate the association between income groups and mortality. Results: Among 1016 patients, the number of patients in each income group was 765 (75.3%) in HIC, 142 (14.0%) in UMIC, and 109 (10.7%) in LLMIC. The management of 200 (19.8%) patients changed from usual care, most commonly delayed surgery. Within 30 days after surgery, 14 (1.4%) patients had a COVID-19 diagnosis and 39 (3.8%) patients died. In the multivariable model, LLMIC was associated with increased mortality (odds ratio 2.83, 95% credible interval 1.37–5.74) compared to HIC. Conclusions: The first wave of the pandemic had a significant impact on surgical decision-making. While the incidence of SARS-CoV-2 infection within 30 days after surgery was low, there was a disparity in mortality between countries and this warrants further examination to identify any modifiable factors