Therapeutic challenges in small cell carcinoma of the larynx.

Primary small cell neuroendocrine carcinoma (SCNC) of the larynx is a rare subtype of laryngeal cancer, accounting for less than 1% of all laryngeal tumours. It most commonly affects smokers in their fifth to sixth decade of life and is characterised by a high incidence of advanced disease at presentation and an aggressive clinical course. Here we present a case of SCNC of the larynx, presenting initially with dysphonia, and an associated literature review collating current knowledge regarding therapeutic approaches. After review of 260 cases in the literature we determined a disease-specific survival of 33.1%. Combined chemoradiotherapy is currently the recommended first-line treatment option.

Primary pulmonary enteric adenocarcinoma presenting as a solitary skull mass.

Pulmonary enteric adenocarcinoma (PEAC) is a rare, aggressive variant of lung adenocarcinoma with early metastatic potential. We present the case of a male smoker in his 50s who presented with right-sided numbness, pain and headache. Imaging revealed a destructive skull base mass invading the right sphenoid sinus. Histopathology was consistent with PEAC. The diagnosis was metastatic PEAC with a distant spread to the skull and represents the first case reported in the literature. We present an associated literature review of the clinical presentation, histological features and management of PEAC with skull metastasis. Metastasis should be considered when evaluating any persistent cranial lesion. Diagnosis requires thorough clinical, radiological and pathological assessment. Treatment involves surgical resection, chemoradiation and targeted therapy. Prognosis directly correlates with clinical stage at presentation. This case highlights the importance of careful evaluation of skull lesions, even in patients without known primary malignancy. Early diagnosis and multimodal therapy may improve outcomes.

Risk factors and management outcomes in epistaxis: a tertiary centre experience.

BACKGROUND: Risk factors and outcomes associated with severe epistaxis are not well understood. This study explores the associations between epistaxis severity, comorbidities, use of antiplatelets or anticoagulants and management outcomes. METHODS: This is a retrospective cross-sectional study of all epistaxis cases presenting to the emergency department at a tertiary academic hospital from January 2016 to December 2019. Epistaxis severity was defined as mild (no intervention), moderate (required cautery and/or packing) and severe (clinical instability with reversal products, surgical or radiological intervention). Univariable and multivariable regression analyses were undertaken, with risk factors and management outcomes analysed according to severity. RESULTS: A total of 543 patients with epistaxis (54.2% male, mean age 74.4 ± 15.7 years) were included in this study, with 14.7% (80) having severe epistaxis. Of these presentations 216 (39.8%) were on antiplatelets, while 207 (38.1%) were on anticoagulants. In univariate analyses, clopidogrel use, hereditary haemorrhagic telangiectasia (HHT), haematological malignancy, bleeding disorders and chronic liver disease (CLD) were associated with moderate to severe epistaxis (P < 0.05), while the use of rivaroxaban was inversely associated severity (P = 0.002). Only HHT, haematological malignancy and CLD remained significant in multivariate models. Cautery as first-line management was infrequently utilized while anticoagulation was frequently withheld. A longer length of stay (1.1 days vs. 4.3 days; P < 0.001) and higher 2-week readmission rates (2.2% vs. 12.5%; P < 0.001) were noted with severe epistaxis compared with mild presentations. CONCLUSION: Epistaxis severity is associated with certain clinical conditions and poor outcomes. Despite recommended guidelines, variations in first-line management were evident.

CENTAUR-The small- and wide-angle neutron scattering diffractometer/spectrometer for the Second Target Station of the Spallation Neutron Source.

CENTAUR has been selected as one of the eight initial instruments to be built at the Second Target Station (STS) of the Spallation Neutron Source at Oak Ridge National Laboratory. It is a small-angle neutron scattering (SANS) and wide-angle neutron scattering (WANS) instrument with diffraction and spectroscopic capabilities. This instrument will maximally leverage the high brightness of the STS source, the state-of-the-art neutron optics, and a suite of detectors to deliver unprecedented capabilities that enable measurements over a wide range of length scales with excellent resolution, measurements on smaller samples, and time-resolved investigations of evolving structures. Notably, the simultaneous WANS and diffraction capability will be unique among neutron scattering instruments in the United States. This instrument will provide much needed capabilities for soft matter and polymer sciences, geology, biology, quantum condensed matter, and other materials sciences that need in situ and operando experiments for kinetic and/or out-of-equilibrium studies. Beam polarization and a high-resolution chopper will enable detailed structural and dynamical investigations of magnetic and quantum materials. CENTAUR's excellent resolution makes it ideal for low-angle diffraction studies of highly ordered large-scale structures, such as skyrmions, shear-induced ordering in colloids, and biomembranes. Additionally, the spectroscopic mode of this instrument extends to lower momentum transfers than are currently possible with existing spectrometers, thereby providing a unique capability for inelastic SANS studies.

Temperature and Sugar Feeding Effects on the Activity of a Laboratory Strain of Aedes aegypti.

Aedes aegypti is an invasive mosquito species that is expected to expand its global distribution through climate change. As poikilotherms, mosquitoes are greatly affected by the temperature of the environment which can impact host-seeking, blood-feeding, and flight activity as well as survival and ability to transmit pathogens. However, an important aspect of mosquito biology on which the effect of temperature has not been investigated is water and sugar-feeding and how access to a sugar source might affect the insect's activity and survival under different thermal conditions. To close this knowledge gap, we relied on actometer experiments to study the activity of both female and male Ae. aegypti at 20 °C, 25 °C, and 30 °C, providing either water or 10% sucrose to the insects. We then measured the total carbohydrate contents of alive mosquitoes using the anthrone protocol. Survival was assessed and compared between all groups. Results from this study will inform on the thermal biology of Ae. aegypti mosquitoes and how access to sugar affects their activity.

Structural Basis for Allosteric Regulation in the Major Antenna Trimer of Photosystem II.

The allosteric regulation of protein function proves important in many life-sustaining processes. In plant photosynthesis, LHCII, the major antenna complex of Photosystem II, employs a delicate switch between light harvesting and photoprotective modes. The switch is triggered by an enlarged pH gradient (ΔpH) across the thylakoid membranes. Using molecular simulations and quantum calculations, we show that ΔpH can tune the light-harvesting potential of the antenna via allosteric regulation of the excitonic coupling in chlorophyll-carotenoid pairs. To this end, we propose how the LHCII excited state lifetime is coupled to the environmental conditions. In line with experimental findings, our theoretical model provides crucial evidence toward the elucidation of the photoprotective switch of higher plants at an all-atom resolution.