Spontaneous Cell Cluster Formation in Human iPSC-Derived Neuronal Spheroid Networks Influences Network Activity

Three-dimensional neuronal culture systems such as spheroids, organoids, and assembloids constitute a branch of neuronal tissue engineering that has improved our ability to model the human brain in the laboratory. However, the more elaborate the brain model, the more difficult it becomes to study functional properties such as electrical activity at the neuronal level, similar to the challenges of studying neurophysiology in vivo. We describe a simple approach to generate self-assembled three-dimensional neuronal spheroid networks with defined human cell composition on microelectrode arrays. Such spheroid networks develop a highly three-dimensional morphology with cell clusters up to 60 μm in thickness and are interconnected by pro-nounced bundles of neuronal fibers and glial processes. We could reliably record from up to hundreds of neurons simultaneously per culture for ≤90 d. By quantifying the formation of these three-dimensional structures over time, while regularly monitoring electrical activity, we were able to establish a strong link between spheroid morphology and network activity. In particular, the formation of cell clusters accelerates formation and maturation of correlated network activity. Astrocytes both influence electrophysiological network activity as well as accelerate the transition from single cell layers to cluster formation. Higher concentrations of astrocytes also have a strong effect of modulating synchronized network activity. This approach thus represents a practi-cal alternative to often complex and heterogeneous organoids, providing easy access to activity within a brain-like 3D environment

Knee cartilage assessment with MRI (dGEMRIC) and subjective knee function in ACL injured copers: a cohort study with a 20 year follow-up.

To assess knee cartilage quality and subjective knee function, 20 years after injury in anterior cruciate ligament (ACL) injured copers

Imaging following acute knee trauma.

Joint injury has been recognized as a potent risk factor for the onset of osteoarthritis. The vast majority of studies using imaging technology for longitudinal assessment of patients following joint injury have focused on the injured knee joint, specifically in patients with anterior cruciate ligament injury and meniscus tears where a high risk for rapid onset of post-traumatic osteoarthritis is well known. Although there are many imaging modalities under constant development, magnetic resonance (MR) imaging is the most important instrument for longitudinal monitoring after joint injury. MR imaging is sensitive for detecting early cartilage degeneration and can evaluate other joint structures including the menisci, bone marrow, tendons, and ligaments which can be sources of pain following acute injury. In this review, focusing on imaging following acute knee trauma, several studies were identified with promising short-term results of osseous and soft tissue changes after joint injury. However, studies connecting these promising short-term results to the development of osteoarthritis were limited which is likely due to the long follow-up periods needed to document the radiographic and clinical onset of the disease. Thus, it is recommended that additional high quality longitudinal studies with extended follow-up periods be performed to further investigate the long-term consequences of the early osseous and soft tissue changes identified on MR imaging after acute knee trauma

An ultra-high-stability four-axis ultra-high-vacuum sample manipulator

A report on a four-axis ultra-high-stability manipulator developed for use at the Veritas and Species RIXS beamlines at MAX IV Laboratory, Lund, Sweden, is presented. The manipulator consists of a compact, light-weight X-Y table with a stiffened Z tower carrying a platform with a rotary seal to which a manipulator rod holding the sample can be attached. Its design parameters have been optimized to achieve high eigen-frequencies via a light-weight yet stiff construction, to absorb forces without deformations, provide a low center of gravity, and have a compact footprint without compromising access to the manipulator rod. The manipulator system can house a multitude of different, easily exchangeable, manipulator rods that can be tailor-made for specific experimental requirements without having to rebuild the entire sample positioning system. It is shown that the manipulator has its lowest eigen-frequency at 48.5 Hz and that long-term stability is in the few tens of nanometres. Position accuracy is shown to be better than 100 nm. Angular accuracy is in the 500 nrad range with a long-term stability of a few hundred nanoradians

Från spårkorridor till ortsnätverk : en planeringsprocess för samhandling på regional nivå

Region Gävleborg och Trafikverket inledde år 2011 ett samarbete om samordnad planering fördubbelspårsutbyggnad av Ostkustbanan. Att vidga samverkan till att innefatta även andrautvecklingsfrågor var därför naturlig. Eftersom ett dubbelspår är den prioriteradeutvecklingsfrågan för regionen och de berörda kommunerna, engagerade sig kustkommunernafrån Sundsvall till Gävle i projektet. Rapporten utgör ett delprojekt i Gävleborgs pilotprojekt ”Pärlband på Spåret – FA Hudiksvall” ochhar som syfte att belysa hur ortssamverkan och samhandling kan medverka till lokal och regionalutveckling. En ny arbetsmodell som baseras på berättelser har prövats

Från spårkorridor till ortsnätverk : en planeringsprocess för samhandling på regional nivå

Region Gävleborg och Trafikverket inledde år 2011 ett samarbete om samordnad planering fördubbelspårsutbyggnad av Ostkustbanan. Att vidga samverkan till att innefatta även andrautvecklingsfrågor var därför naturlig. Eftersom ett dubbelspår är den prioriteradeutvecklingsfrågan för regionen och de berörda kommunerna, engagerade sig kustkommunernafrån Sundsvall till Gävle i projektet. Rapporten utgör ett delprojekt i Gävleborgs pilotprojekt ”Pärlband på Spåret – FA Hudiksvall” ochhar som syfte att belysa hur ortssamverkan och samhandling kan medverka till lokal och regionalutveckling. En ny arbetsmodell som baseras på berättelser har prövats

Association between delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and joint space narrowing and osteophytes: a cohort study in patients with partial meniscectomy with 11 years of follow-up.

To examine the association between the relaxation time (T1Gd) of delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and grade of tibiofemoral joint space narrowing (JSN) and osteophytosis 11 years later, in a cohort of meniscectomized patients

Longitudinal assessment of femoral knee cartilage quality using contrast enhanced MRI (dGEMRIC) in patients with anterior cruciate ligament injury - comparison with asymptomatic volunteers.

OBJECTIVE: In this observational longitudinal study we estimate knee joint cartilage glycosaminoglycan (GAG) content, in patients with an acute anterior cruciate ligament (ACL) injury, with or without a concomitant meniscus injury. METHODS: 29 knees (19 men/10 women) were prospectively examined by repeat delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), approximately 3 weeks and 2.3±1.3 (range 4.5) years after the injury. We estimated the GAG content (T1Gd) in the central weight-bearing parts of the medial and lateral femoral cartilage and compared results with a reference cohort (n=24) with normal knees and no history of injury examined by dGEMRIC at one occasion previously. RESULTS: The healthy reference group had longer T1Gd values compared with the ACL-injured patients at follow-up both medially: 428±38 vs 363±61ms (P<0.0001) and laterally: 445±41 vs 396±48ms (P=0.0002). At follow-up T1Gd was lower in meniscectomized patients compared to those without a meniscectomy, both medially (-84ms, P=0.002) and laterally (-38ms, P=0.05). In the injured group, the medial femoral cartilage showed similar T1Gd at the two dGEMRIC investigations: 357±50 vs 363±61ms (P=0.57), whereas the lateral femoral cartilage T1Gd increased: 374±48 vs 396±48ms (P=0.04). CONCLUSIONS: The general decrease in cartilage T1Gd in ACL-injured patients compared with references provide evidence for structural matrix GAG changes that seem more pronounced if a concomitant meniscal injury is present. The fact that post-traumatic OA commonly develops in ACL-injured patients, in particularly those with meniscectomy, suggests that shorter T1Gd may be an early biomarker for OA

Association of knee pain and different definitions of knee osteoarthritis with health-related quality of life : A population-based cohort study in southern Sweden

Background: While the impact of knee pain and knee osteoarthritis (OA) on health-related quality of life (HRQoL) has been investigated in the literature, there is a lack of knowledge on the impact of different definitions of OA on HRQoL. The main aim of this study was to measure and compare the impact of knee OA and its different definitions on HRQoL in the general population. Methods: A random sample of 1300 participants from Malmö, Sweden with pain in one or both knees in the past 12 months with duration ≥4 weeks and 650 participants without were invited to clinical and radiographic knee examination. A total of 1527 individuals with a mean (SD) age 69.4 (7.2) participated and responded to both generic (EQ-5D-3L) and disease-specific (the Knee injury and Osteoarthritis Outcome Score) questionnaires. Knee pain was defined as pain during the last month during most of the days. Knee OA was defined radiographically (equivalent to Kellgren and Lawrence grade ≥2) and clinically according to the American College of Rheumatology (ACR) criteria. Results: Of participants with either knee pain or knee OA or both, 7 % reported no problem for the EQ-5D-3L attributes. The corresponding proportion among references (neither knee pain nor OA) was 42 %. The participants with knee pain and OA had all HRQoL measures lower compared to those with knee pain but no OA. The ACR clinical definition of knee OA was associated with lower HRQoL than the definition based on radiographic knee OA (adjusted difference -0.08 in UK EQ-5D-3L index score). Conclusions: Applying different definitions of knee OA result in different levels of HRQoL and this is mainly explained by the knee pain experience. These differences may lead to discrepant conclusions from cost-utility analyses

Searching for the neurite density with diffusion MRI : Challenges for biophysical modeling

In vivo mapping of the neurite density with diffusion MRI (dMRI) is a high but challenging aim. First, it is unknown whether all neurites exhibit completely anisotropic (“stick-like”) diffusion. Second, the “density” of tissue components may be confounded by non-diffusion properties such as T2 relaxation. Third, the domain of validity for the estimated parameters to serve as indices of neurite density is incompletely explored. We investigated these challenges by acquiring data with “b-tensor encoding” and multiple echo times in brain regions with low orientation coherence and in white matter lesions. Results showed that microscopic anisotropy from b-tensor data is associated with myelinated axons but not with dendrites. Furthermore, b-tensor data together with data acquired for multiple echo times showed that unbiased density estimates in white matter lesions require data-driven estimates of compartment-specific T2 values. Finally, the “stick” fractions of different biophysical models could generally not serve as neurite density indices across the healthy brain and white matter lesions, where outcomes of comparisons depended on the choice of constraints. In particular, constraining compartment-specific T2 values was ambiguous in the healthy brain and had a large impact on estimated values. In summary, estimating neurite density generally requires accounting for different diffusion and/or T2 properties between axons and dendrites. Constrained “index” parameters could be valid within limited domains that should be delineated by future studies