Functional MRI Readouts From BOLD and Diffusion Measurements Differentially Respond to Optogenetic Activation and Tissue Heating

Functional blood-oxygenation-level-dependent (BOLD) MRI provides a brain-wide readout that depends on the hemodynamic response to neuronal activity. Diffusion fMRI has been proposed as an alternative to BOLD fMRI and has been postulated to directly rely on neuronal activity. These complementary functional readouts are versatile tools to be combined with optogenetic stimulation to investigate networks of the brain. The cell-specificity and temporal precision of optogenetic manipulations promise to enable further investigation of the origin of fMRI signals. The signal characteristics of the diffusion fMRI readout vice versa may better resolve network effects of optogenetic stimulation. However, the light application needed for optogenetic stimulation is accompanied by heat deposition within the tissue. As both diffusion and BOLD are sensitive to temperature changes, light application can lead to apparent activations confounding the interpretation of fMRI data. The degree of tissue heating, the appearance of apparent activation in different fMRI sequences and the origin of these phenomena are not well understood. Here, we disentangled apparent activations in BOLD and diffusion measurements in rats from physiological activation upon sensory or optogenetic stimulation. Both, BOLD and diffusion fMRI revealed similar signal shapes upon sensory stimulation that differed clearly from those upon heating. Apparent activations induced by high-intensity light application were dominated by T2∗-effects and resulted in mainly negative signal changes. We estimated that even low-intensity light application used for optogenetic stimulation reduces the BOLD response close to the fiber by up to 0.4%. The diffusion fMRI signal contained T2, T2∗ and diffusion components. The apparent diffusion coefficient, which reflects the isolated diffusion component, showed negative changes upon both optogenetic and electric forepaw stimulation. In contrast, positive changes were detected upon high-intensity light application and thus ruled out heating as a major contributor to the diffusion fMRI signal

The effects of a varus unloader brace for lateral tibiofemoral osteoarthritis and valgus malalignment after anterior cruciate ligament reconstruction: A single case study

We investigated the immediate effects of a varus knee brace on knee symptoms and knee-joint biomechanics in an individual with predominant lateral tibiofemoral joint osteoarthritis (TFJOA) and valgus malalignment after anterior cruciate ligament (ACL) reconstruction. A varus unloader brace was prescribed to a 48-year-old male with predominant lateral radiographic and symptomatic TFJOA and valgus malalignment eight-years following ACL reconstruction. During a step-down task, the participant rated knee pain, task-difficulty, knee-stability and knee-confidence on four separate visual analogue scales. Quantitative gait analysis was conducted during self-selected walking trials under three test conditions in a randomized order: (i) no brace; (ii) brace without frontal plane adjustment (no varus re-alignment); and (ii) brace with frontal plane adjustment (varus re-alignment). Post-processing of gait data involved calculation of knee kinematics and net joint moments for the reconstructed limb. The participant reported improved pain (3%), task difficulty (41%), stability (46%) and confidence (49%) when performing the step-down task with the brace. The varus brace resulted in immediate reductions in knee abduction angle (24%) and internal rotation angle (56%), and increased knee adduction moment (18%). These findings provide preliminary evidence for potentially beneficial effects of bracing on knee-symptoms and biomechanics in individuals with lateral TFJOA after reconstruction

UK Head and neck cancer surgical capacity during the second wave of the COVID—19 pandemic: Have we learned the lessons? COVIDSurg collaborative

Objectives The aim of this study was to evaluate the differences in surgical capacity for head and neck cancer in the UK between the first wave (March-June 2020) and the current wave (Jan-Feb 2021) of the COVID-19 pandemic. Design REDcap online-based survey of hospital capacity. Setting UK secondary and tertiary hospitals providing head and neck cancer surgery. Participants One representative per hospital was asked to report the capacity for head and neck cancer surgery in that institution. Main outcome measures The principal measures of interests were new patient referrals, capacity in outpatients, theatres and critical care; therapeutic compromises constituting delay to surgery, de-escalated surgery and therapeutic migration to non-surgical primary modality. Results Data were returned from approximately 95% of UK hospitals with a head and neck cancer surgery specialist service. 50% of UK head and neck cancer patients requiring surgery have significantly compromised treatments during the second wave: 28% delayed, 10% have received radiotherapy-based treatment instead of surgery, and 12% have received de-escalated surgery. Surgical capacity has been more severely constrained in the second wave (58% of pre-pandemic level) compared with the first wave (62%) despite the time to prepare. Conclusions Some hospitals are overwhelmed by COVID-19 and unable to offer essential cancer surgery, but all have neighbouring hospitals in their region retaining good (or even normal) capacity. It is noteworthy that very few patients have been appropriately redirected away from the hospitals most constrained by their burden of COVID-19. The paucity of an effective central or regional strategic response to this evident mismatch between demand and surgical capacity is to the detriment of our head and neck cancer patients

HPV-Associated Head and Neck Cancer: Molecular and Nano-Scale Markers for Prognosis and Therapeutic Stratification

Over the last 10 years, it has become clear that patients with head and neck cancer can be stratified into two distinct subgroups on the basis of the etiology of their disease. Patients with human papillomavirus-related cancers have significantly better survival rates and may necessitate different therapeutic approaches than those with tobacco and/or alcohol related cancers. This review discusses the various biomarkers currently in use for identification of patients with HPV-positive cancers with a focus on the advantages and limitations of molecular and nano-scale markers